Ann Welzein is Karl's ex-wife. They have three kids together, two daughters and a son. At one point Karl references a son (Chad) and two daughters (Jillian & ?).
They met in high school, when she had the "third biggest boobs in school." They were still married when Karl started using Twitter. Eventually she kicked him out of the house and he moved in with Dave. Karl finally signed divorce papers in 2012.
On December 2nd, 2010 Ann was pronounced dead in a car crash: "Ann died in a car accident this morning. Pretty shook up over here.". The next day, Karl clarified that it was Dave playing a joke because Karl left his twitter page open when he went to work.