Cuddyer will try to stretch his streak to 26 games and hand the Giants their longest skid in three seasons Saturday.
Cuddyer is batting .381 with six homers and 18 RBIs during his lengthy run, but Colorado (40-41) has posted a 10-15 record. The Rockies had also dropped 11 of 15 before Friday's series opener against San Francisco (38-41).
His two-run homer in the third inning helped deliver a 4-1 victory over the Giants and sent them to a season high-tying fifth consecutive defeat.
"Cuddy's so locked in right now, I don't know if you can swing the bat any better than he is right now," manager Walt Weiss said. "He's doing damage, too, when he gets his hits. He's been huge."
The loss put San Francisco on the verge of its first six-game skid since it dropped seven in a row June 26-July 2, 2010. It was also San Francisco's sixth in a row on the road, one shy of matching its season high.
The Giants' seven-game road losing streak from May 17-June 1 started with back-to-back defeats against Colorado.
Matt Cain (5-4, 4.54 ERA) will try to help his team avoid matching that skid while earning a seventh win in as many starts against the Rockies. He yielded two runs and two hits over five innings in his most recent matchup, a 7-3 victory May 26, but wasn't nearly as dominant in his only start in Denver this season.
The right-hander gave up six runs - on three homers - in 6 1-3 innings May 16 but he got enough support for an 8-6 win. He's 2-1 in his last three starts at Coors Field despite an 8.44 ERA over that stretch.
Cain has received a combined 43 runs of support in his last six starts against Colorado but has gotten 14 in his five outings this month. He has gone 1-1 in his last four games despite a 2.03 ERA, 25 strikeouts and five walks over that span.
Cain gave up three runs over six innings, struck out eight and walked none Sunday but took the loss in a 7-2 defeat to Miami.
"We didn't get the job done. We didn't get some guys in when we needed to and we didn't throw the ball like we needed to," he said. "You just have to say it's over with and move on."
Colorado's Jorge De La Rosa (8-4, 3.19) had also struggled to get run support recently until a 7-6 win at Washington on Sunday. The left-hander has a 2.74 ERA in his last seven starts but had gotten zero runs in each of his previous two.
He gave up one hit in seven scoreless innings June 17 in a 2-0 loss in Toronto and allowed two runs over six innings Sunday.
De La Rosa snapped a three-game losing streak to San Francisco on May 17 despite giving up five runs over five innings. The Rockies scored nine runs during his five frames en route to a 10-9 victory and have won five of the past seven games in the series.
Cuddyer, batting hitting .352 in his career against San Francisco, hit a two-run double his only matchup with Cain on May 26. He was on the disabled list for a bulging disk in his neck during Cain's most recent game in Denver.