Maria Luisa brachte vier Kinder auf die Welt: 1. ihren Sohn Ludwig I., geboren am 25. August 1707 und gestorben am 31. August 1724; 2. ihren Sohn Philipp, geboren am 2. Juli 1709 und gestorben am 8. Juli 1709; 3. ihren Sohn Philipp, geboren am 7. Juni 1712 und gestorben am 29. Dezember 1719; und 4. ihren Sohn Ferdinand VI., geboren am 23. September 1713 und gestorben am 10. August 1759. Ihr erster und ihr vierter Sohn wurden beide Könige von Spanien. Philipp V. hatte am 15. Januar 1724 als König von Spanien abgedankt, und Ludwig I. bestieg als der nächste König den spanischen Thron. Seine Regierungszeit währte alllerdings nur sieben Monate, da er sich die Pocken zugezogen hatte und starb. Nach seinem Tod wurde sein Vater Philipp V. wieder König von Spanien. Ferdinand VI. bestieg den spanischen Thron nach dem Tod des Vaters im Jahr 1746 und regierte bis zu seinem eigenen Tod im Jahr 1759.
Ihre erste Schwangerschaft zeigte sich, wie bei uns normalsterblichen Frauen, durch die Vorliebe besonderer Speisen. So lesen wir in zwei Briefen der Prinzessin des Ursins an Madame de Maintenon, datiert auf den 23. Januar und 30. Januar 1707: "... that her Majesty [Maria Luisa], who in general does not like high seasoned dishes nor salt food, eats heartily of oysters, which she disliked formerly: whether these are favourable prognostics or not, we shall know the result very soon [ob sie also schwanger ist]. ... It is no longer permitted to doubt of the Queen's pregnancy, without offending the whole faculty, which is not my intention, for they assure me that her Majesty has all its symptoms, and that which appears to me the strongest, is her increase in size about the waist; her appetite, which also increases, convinces me still more of the fact. The King spoke of it yesterday to his ministers in his apartment, and so did I in my quarto chico, to all the courtiers who frequent it, which caused inexpressible transports of joy. The people run about the streets like madmen, singing and talking all the nonsense that comes into their heads." (in: The Secret Correspondence of Madame de Maintenon with the Princess des Ursins, Volume II, London 1827, pp. 306-307).
An was man alles denken muss, wenn die Geburt eines königlichen Kindes bevorsteht: Brief der Prinzessin des Ursins an Madame de Maintenon, datiert auf den 4. Februar 1707: "It therefore now becomes necessary to exercise our foresight and precaution for her Majesty [Maria Luisa], and for the child which it shall please God to send us; and it is no trifling charge for me, to whom this duty is solely confided, their Majesties relying upon my zeal and fidelity. You will doubtless be surprised, that, reasoning with me as they do, upon the choice that is to be made of a governess, we cannot prevail on ourselves to come to a determination. The chief quality of such a person is, in my opinion, fidelity. In general, I am inclined to think that all the widows of grandees who may aspire to this charge, are incapable of a bad action: but it is, as it were, impossible to answer for their intentions, the greatest part of them keeping very much aloof, and being related to grandees whom we have reason to believe attached to the house of Austria. We are not less embarrassed about a nurse. The health of males and females, amongst the nobility as well as the plebeians, being very bad, almost all the children are born with hereditary complaints ... The Biscayans appear to me the most healthy of his Majesty's subjects ... the cold air of the mountains which they inhabit rendering them fair, fresh, and robust ... Their milk must give a nourishment which will inspire gaiety in the Prince of Asturias [man erwartet also einen Prinzen]. We must have nothing melancholy in his temperament ... I have had a long conversation today with all the faculty ... in order that from the present time they may carefully seek for pregnant women of good character ... The King of Spain [Philipp V.] wishes that a medical man should attend the Queen in her confinement, thus dispensing with etiquette in that respect; because he thinks that surgeons are more skilful than midwives ... you will, therefore, Madam [de Maintenon], have the goodness to mention it to the King [Ludwig XIV.] and the Duchess of Burgundy [die Schwester von Maria Luisa], for probably it will be the person she has employed that will be sent to us. Would it not be proper that he should come here three months before the Queen has completed her time, since there are many instances of women who have been confined in their seventh month, and in that case it would be wrong if he were not upon the spot? ... The Prince or Princess that we expect, and that we ought so ardently to desire, for the tranquillity of the two monarchies [Spanien und Frankreich im Spanischen Erbfolgekrieg], might possibly disappoint our wishes if the Queen should be in a state of agitation, and I foresee that she will not recover from it if the King leaves her to join the army. ..." (in: The Secret Correspondence of Madame de Maintenon with the Princess des Ursins, Volume II, London 1827, pp. 309-311).
In einem Brief der Prinzessin des Ursins, datiert auf den 7. November 1707, lesen wir über Maria Luises ersten Sohn, Ludwig I., der gerade einmal etwas über zwei Monate alt ist: "Our Prince of Asturias [Ludwig I.] is very well, and begins to laugh, and look a perfect beauty; his nurse gives excellent milk, but we have nevertheless sent for four of the others to return, in order not to be at a loss, in case any misfortune happen to her." (in: The Secret Correspondence of Madame de Maintenon with the Princess des Ursins, Volume III, London 1827, p. 122).
Die Geburt ihres zweiten Kindes, beschrieben in einem Brief der Prinzessin des Ursins, datiert auf den 2. Juli 1709: "The Queen [Maria Luisa] has just been confined, and has experienced much more difficulty than the first time; the appearance of the child would induce a belief that she has not gone her full time [es war also eine Frühgeburt]; it made no effort, and Clement [der Arzt], in a word, doubts whether it will live; we attribute this misfortune to the agitation of her Majesty since yesterday evening, when it was perceived that the Prince of Asturias [ihr erster Sohn] had the small-pox. Her Majesty only consulted her feelings on this occasion, and whatever we said, she neither thought of herself nor of the child unborn. There was, however, no ground for her fears, since the small-pox of the Prince is of a mild kind, and not in the least dangerous. I am so much affected at the great sufferings of the Queen, that I cannot add more, nor even do myself the honour of writing to the King. I beg you [Madame de Maintenon] to represent this to his Majesty." In einem Brief vom 5. Juli 1709 der Prinzessin des Ursins erfahren wir Folgendes über das zweite Kind, den Prinzen Philipp: "... I have had the honour of communicating to you the Queen's confinement, and the poor hopes we had of preserving the life of the infant; but our opinion is changed, and it is probable that this little Prince will not die, because he takes to the breast, sleeps very well, and performs all his other functions. His brother is almost cured of the small-pox, although he had a pretty good share of it. ... Her Majesty is as well as it is possible for her to be ... She dare not, she says, ask for the infant to be brought to her, to see it, for fear of loving and losing it: it is very pretty, more especially its mouth, which is astonishingly small. ..." (in: The Secret Correspondence of Madame de Maintenon with the Princess des Ursins, Volume III, London 1827, pp. 301-305). Aber in einem Brief vom 9. Juli 1709 lesen wir: "The ray of hope which we had of preserving the life of the infant soon vanished; he was seized with convulsions last evening, and the little angel went to heaven a little before midnight [am 8. Juli 1709]. Although there was but little hope of his getting the better of his weakness, and being cured of a tumour which he had, there was some ground for it, so long as he took to the breast as well as he did ..."