Based on the real-life courtship between Kumail Nanjiani and Emily V. Gordon, "The Big Sick" tells the story of Pakistan-born aspiring comedian Kumail, who connects with grad student Emily after one of his standup sets. However, what they thought would be just a one-night stand blossoms into the real thing, which complicates the life that is expected of Kumail by his traditional Muslim parents.

When Emily is beset with a mystery illness, it forces Kumail to navigate the medical crisis with her parents, Beth and Terry, who he's never met, while dealing with the emotional tug-of-war between his family and his heart.