The loss extended the Phillies' losing streak to five. The loss also dropped Philadelphia to 4-11 in Cliff Lee's starts this season.
Lee allowed three runs – two earned – and nine hits in six innings.
Ahead 3-1, Colorado broke the game open in the seventh, when it added three runs off reliever Michael Schwimer.
The Phillies have lost 11 of their past 12 games and now sit 15 games behind the NL East leading Nationals.
Perhaps what's even more telling is that the Phillies have just four more wins than the hapless Houston Astros, the worst team in the NL.
"I shake my head because I look out there and see Lee pitching. I can't believe we can't win some games with him pitching. We got outplayed," Manuel said.
The two clubs resume their three-game set on Saturday with Vance Worley (4-5, 3.54) opposing Jeremy Guthrie (3-8, 6.05).
- Patrick Gordon is the editor of the Philadelphia Baseball Review. Contact him at pgordon@philadelphiabaseballreview.com or @Philabaseball on Twitter.