Incumbent Senator Ben Nighthorse Campbell (first elected in 1992 as a Democrat and re-elected in 1998 as a Republican, having switched parties in 1995) retired instead of seeking a third term.

On March 3, 2004, incumbent Republican Senator Ben Nighthorse Campbell announced that he would not seek reelection due to health concerns, having recently been treated for prostate cancer and heartburn.

After Campbell's retirement, many expected popular Republican Governor Bill Owens to enter the race,[2] however he declined to run.

Campbell's retirement and Owens' decision not to run prompted a number of prominent Democrats to reexamine the race.

According to the Rocky Mountain News, Coors described his company's pro-LGBT practices as "good business, separate from politics.