Guyer was hit three times by pitches, all thrown by Mark Buehrle, tying a major league record and extending his club record for a season to 24.
"It is frustrating at times because I want to hit, but it's my natural instinct to stay in there so I can't do anything about it," said Guyer, who walked in his only other plate appearance.
"He's not trying to hit me. He's trying to come in hard with cutters, and he missed a little bit. Some other batters might move their leg to get out of the way, but I don't know how to do that," he said.
The loss left the Rays at 78-82.
Troy Tulowitzki doubled and singled in returning to the Toronto lineup after missing three weeks with injuries.
Tulowitzki went 2 for 5 and scored a run. Earlier in the day, the star shortstop homered and doubled twice in a simulated game against Toronto minor league pitchers at Tropicana Field.
Buehrle (15-7) gave up four runs and six hits in 6 2-3 innings. He is two innings away from reaching 200 for the 15th consecutive season.
Tulowitzki hadn't played since Sept. 12, when he cracked his scapula and bruised muscles in his upper back after colliding with outfielder Kevin Pillar in a game against the New York Yankees.
Blue Jays manager John Gibbons plans to give Tulowitzki Saturday night's game off and then have him play in Sunday's regular-season finale against the Rays.
Mikie Mahtook hit a three-run homer off Buehrle to complete a four-run fifth that gave the Rays a 4-1 lead, but the lead was gone by the time the Rays got up to bat again.
"We talk about shutdown innings. That (sixth) would have been a nice time to get a shutdown inning. We did not," Rays manager Kevin Cash said. "We misplayed a couple balls in the outfield. We just made some young mistakes . . . it just wasn't very pretty."
FORSYTHE CHOSEN RAYS MVP
Second baseman Logan Forsythe, who started the season as a utility player, was chosen the Rays most valuable player by the Tampa Bay Chapter of the Baseball Writers Association of America. Forsythe is hitting .281 with 17 home runs and 68 RBIs.
Rays: C Curt Casali, out since Aug. 26 with a strained left hamstring, will not play again this season.