One persistent rumor is that Pressly married a man named Brodie Mitchell in 1998. Pressly, who has never married, has stated she has heard of Mitchell but does not know him.

Pressly dated her Jack and Jill co-star Simon Rex in 2000 and 2001. In a December 10, 2001 radio interview with Howard Stern, she said that Rex broke up with her on her birthday.

In October 2006, she became engaged to her boyfriend of a year-and-a-half, DJ Eric Calvo (aka DJ Eric Cubiche), with whom she had been friends for nine years. Pressly gave birth on May 11, 2007 at 7:31 a.m. in Cedars-Sinai Medical Center to their first child, Dezi James Calvo, who weighed 6 lb 4 oz (2.8 kg), and was 18 1/2 inches long. In a February 2007 interview on The Tonight Show With Jay Leno, Pressly said she wants the child to be bilingual (English/Spanish) to reflect Calvo's Cuban heritage.

Pressly said in a 2006 interview with Esquire magazine that she almost purchased a ticket for a flight