During the 2002 Wyoming gubernatorial election, Karpan endorsed Paul Hickey for the Democratic nomination. She supported Hillary Clinton during the 2008 Wyoming Democratic presidential caucuses and served as a Clinton delegate at the party's national convention. During the 2010 Wyoming gubernatorial election, Karpan served as co-chair of Leslie Peterson's gubernatorial campaign alongside Joe Evans. She again supported Clinton during the 2016 Democratic presidential primaries. In the same year, Karpan served as the state chair of Ryan Greene's House of Representatives campaign.