Worked as a procurement officer at the National Security Agency (NSA) at Fort Meade in Laurel, Maryland from college graduation in 1986 until 1992.
Came out as gay on November 15, 2008, at a pro-gay marriage rally in Las Vegas hosted by the LGBT (Lesbian, Gay, Bisexual, and Transgender) Center of Southern Nevada. At that rally, she also publicly announced for the first time that she has a wife, to whom she was married in California on October 25, 2008.
Her partner, Alex, gave birth to twins, a boy Lucas Claude and a girl Olivia Lou, on April 27, 2009.
Made history as the first African-American master of ceremonies at the White House Correspondents' dinner. 
In September 2011, Sykes revealed that earlier in the year, she had gone in for breast reduction surgery and discovered that she had very early-stage breast cancer. Because of a history of breast cancer in her family, she decided to have a bilateral mastectomy (both breasts removed).