The novel delves into the reactions of Sebastian's family and friends as his reliance on alcohol intensifies. At first, Sebastian is portrayed as a typical college student who enjoys drinking but limits it to social occasions without facing significant consequences. However, Charles notices a change in Sebastian's drinking behavior and generally upbeat nature after they return to Oxford following a delightful summer at the Brideshead estate.

A series of events highlight the decline in the close friendship between Charles and Sebastian. After attending a party in London, Sebastian drives under the influence with several passengers, including Charles. They are stopped by the police and taken into custody. During Easter at Brideshead, Sebastian's excessive drinking causes him to skip meals and mistreat Charles. He accuses Charles of spying on him for the family and eventually leaves for London.

The family's reaction to Sebastian's alcoholism is a classic example of denial. During Easter, none of the family members directly address Sebastian's issues, instead relying on Charles to manage the situation. Lady Marchmain questions Charles about Sebastian's behavior, and Charles, protecting his friend, claims Sebastian is just catching a cold. Julia confesses to Charles that she knows about her brother's drinking but insists that Charles take responsibility. "Well, you must deal with him. It's no business of mine," she says. Brideshead also asks Charles to help get Sebastian to stop drinking, and Lady Marchmain expects Charles to keep a close watch on him. "You've got to help him. I can't," she pleads.

Eventually, a dean finds Sebastian wandering the university grounds, intoxicated. The school agrees to let him stay if he consents to live with a monsignor (a member of the Roman Catholic clergy), but Sebastian resolutely refuses. As a result, Sebastian leaves Oxford and embarks on a trip to the Middle East with Mr. Samgrass as his guardian, arranged by his mother. This journey, rather than helping him, leads Sebastian into a lifelong pattern of drinking and drifting across the Middle East and North Africa. After Sebastian departs from Oxford, his encounters with Charles become infrequent.