Hiroki has suffered for years from an unknown illness. Due to his weak constitution, he is unable to live like a normal schoolkid and often has to depend on his best friend Ayano to take care of him. When he can attend school, he often spends most of his time in the nurse's office. Ayano cares for Hiroki more than she is willing to admit, and Hiroki repeatedly pushes her away due to his embarrassment at being unable to "be a man" and fend for himself.
One day, an outlandishly-dressed girl named Maria drops in, and cheerfully tells Hiroki that she is to be his private nurse for one month. Maria will live with Hiroki, give him her personal care, and help cure him. Hiroki is bullheaded and doesn't want to lose what freedom he has, and Ayano has mixed emotions about a beautiful girl living with her lifelong friend. Over the course of that month, a romance begins to blossom -- but with whom?
Private Nurse plays as an interactive novel. The story proceeds at its own pace, pausing occasionally to allow the user to intervene by making a decision, resulting in a plot branch. The game features multiple endings, and countless CG illustrations.
The game includes graphic depictions of consensual sex, and is for adults only.