Five days after allowing just one hit in five shutout innings, Rodriguez (0-1) gave up five runs and eight hits in five innings as Cincinnati beat the Astros 6-1.
Rodriguez was doomed by two home runs as Reds starter Travis Wood hit a three-run homer off Rodriguez in the third, and Ramon Hernandez followed with a two-run shot in the fourth.
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"I think you saw how quickly they jumped on some pitches early in the count or first pitch or second pitch," Houston manager Brad Mills said. "They weren't letting him get ahead. That was one of the biggest things last week was he was getting ahead."
Rodriguez said through a translator that he didn't underestimate Wood (2-3).
"I missed the pitch," he said. "I was trying to throw it low and inside, but it stayed in the middle high. The first three innings I was really good, but after that, I missed a lot of pitches."
Houston's offense couldn't get going on Monday. The Astros stranded nine baserunners, including five in scoring position. Houston left runners in scoring position in the first, fifth, seventh and left the bases loaded in the eighth.
Hunter Pence went 2 for 4 with a triple and a home run in the eighth to lead the way for Houston.
"Offensively, we tried to battle and come back," Mills said. "I know we had a lot of guys in scoring position. We've been able to get that hit to get us back in the game, but tonight it didn't happen. With those runners in scoring position, [Wood] was able to make some pitches to keep us from getting those hits that would let us climb back into it."
Astros second baseman Bill Hall was hit by a pitch in the eighth inning. He said it got him a little in the ribs, but he would be fine.
Hall, who went 1 for 3 with a double, was impressed with Wood, who threw 6 2/3 shutout innings, allowing six hits with six strikeouts.
"They got him a lead, and it's a little bit easier to pitch with a lead than in a close ball game where you feel that one swing of the bat can hurt you," Hall said. "He's not a pitcher that gives up a lot of walks. He pitches well. He stayed away from the big inning. That's what you have to do. That early lead let him relax a little bit, and he made some pitches."
Wood had retired six straight when Clint Barmes singled with one out in the fifth inning. Pinch hitter Matt Downs singled after that, but Wood retired the next two to end the inning.
He pitched a perfect sixth before he was chased with a single by Angel Sanchez with two outs in the seventh. Wood walked Brett Wallace to start that inning and got some help from Brandon Phillips when he robbed Chris Johnson of a hit with a nifty diving catch that ended in a belly flop for the first out.
Reliever Bill Bray gave up a single to Michael Bourn to load the bases before he was replaced by Logan Ondrusek, who retired J.R. Towles to end the inning.
Pence tripled with two outs in the first inning, but Carlos Lee struck out to end that threat.
Houston designated RHP Nelson Figueroa for assignment and recalled LHP Sergio Escalona from Triple-A Oklahoma after the game. ... Mills said he expects Lyon's stint on the disabled list to stretch longer than 15 days. He went on the disabled list on Thursday with tendinitis in his biceps and a partial tear in his rotator cuff, which can heal without surgery. Mills said after the swelling subsides, it will take some time for him to build back his arm strength enough to return, but gave no indication of how much longer than 15 days that could take.