The film Sex And Death 101 is a film about Roderick Blank, an executive who is about to be married to his fiancé. At his bachelor party he receives an email with list of 101 women. He realized his fiancé was number 29. He thinks it is just a prank list until he meets Carlotta Valdez and sleeps with her which is number 30 on the list. He then realizes that the list is all his sexual encounters from the past to future.
Roderick then cancels his wedding and starts to sleep with the ladies on the list. His friends convince him to bury the list. He then falls for Lester, a quirky veterinarian. However, she died. He digs back the list and continues his sleeping rampage.
One day, Roderick gets shocked when he learns the last name on his list is Gillian de Raisx, a female vigilante better known as Death Nell. Death Nell seduces men then puts them into a coma.
Roderick decides to abandon the list again. However, after an incident he ends up at a Catholic college. The women think he was sent there to deflower them. He tries to resist but fails in the end. He jumps from 82 to 100 in that single event.
Roderick gets to thinking that he might not survive after Death Nell. He tries to sleep with another Gillian de Rasx in Australia. However, he decides that has to face the consequences of his doings and decides to find the real Death Nell.
Roderick and Gillan meet over dinner. Gillian shares everything with Roderick, her profession, her marriage and her "side-job". She also tells Roderick that she is exhausted with her mission. In the end, they both took a sedative pill and lay on the bed with the words written on the wall 'The End'.
In the epilogue of the movie, it revealed that they both survived the pills. They got married and have a child.