The result was a 6-5 loss Wednesday, giving Cincinnati both legs of a two-game set against an A's team that has dropped three straight series and fallen into a first-place tie in the American League West with the Rangers, who have won nine of their past 10 games.
Colon allowed five runs, putting an end to his remarkable stretch of 15 straight quality starts. He also gave out three free passes and has now walked at least two in each of his past three outings after not issuing more than one in his previous five.
"He didn't look like he had his best stuff today," manager Bob Melvin said. "His velocity was down. He did have a little bit of a stomach ailment in the bullpen when he was warming up. He's had it before, so it was just a combination of things today.
"He's also able to pitch without his best stuff at times. This is the first time we have not seen him do that."
But Colon refused to use any bit of illness as an excuse, simply saying through translator Ariel Prieto, "I need to pitch better. I wasn't throwing strikes."
"It looked like his velocity was down," said Josh Reddick. "You can't really 100 percent tell, but he didn't look like himself today, didn't look like his stuff was breaking like it normally does. Obviously he got hit around, and we're not used to seeing that."
It's possible Colon is tiring, having already racked up 150 1/3 innings this year. That ranks 11th in the American League for a pitcher who celebrated his 40th birthday back in May.
But he won't use that to justify his poor outing, either.
"It's no excuse," Colon said. "I still have to work hard to stay strong and do the same thing I did in the first half."
"I think that's probably a concern any time when you get deep in a season with him," Melvin said.
No matter, the timing couldn't be worse for the A's, who have not only already optioned Tommy Milone to Triple-A, but have watched a few of their other starters, namely A.J. Griffin and Dan Straily, also struggle to be consistent.
A's starters posted a 3.62 ERA before the break. Since, they have a 4.53 ERA, including a 5.57 ERA in the last 12 games.
Those woes, combined with a spotty offensive showing, have the A's at 8-10 since the break.
At least they have to be encouraged by their improved approach at the plate Wednesday, particularly with runners in scoring position. The A's were 4-for-9 in such situations in the Cincinnati finale after going 4-for-42 with runners in scoring position in their previous six games.
"That would have been an easy game to just hang your head and say, 'Here we go again,' but they didn't, and we had some of our best at-bats we've had in a while," Melvin said, "So you try to take something positive from that."
Josh Donaldson led the way with two RBIs, his first since the break. Oakland's third baseman, who entered the day batting .189 in that time, launched a two-out solo shot to right field off Homer Bailey in the second and added an RBI single in a three-run sixth.
Eric Sogard contributed a two-run triple in the frame, with Stephen Vogt having already gotten involved with an RBI base hit in the fourth that scored Brandon Moss and nearly Alberto Callaspo, who was tagged out at the plate and suffered a left forearm contusion.
"This is a good ballpark to hit in," Donaldson said. "I had a couple decent pitches to hit today and was able to take advantage of them.
"That's what it's going to take, somebody to step up with guys in scoring position to get it done. Then everyone can kind of relax a little bit and stay within themselves."
But none of it was enough to erase the damage left by Colon, who threw 67 pitches before being replaced by righty Jesse Chavez. Oakland's righty reliever proceeded to give up one run on three hits in 2 1/3 innings.
"I didn't do a great job," said Colon, "but I believe if they keep hitting that way, we're going to win pretty soon."