The Baltimore Sun's Eduardo A. Encina reported Donaldson appeared to be holding his right calf.
This is another setback for Donaldson after he dealt with a calf injury earlier in the season. Still, he has been durable in recent years and played more than 150 games in each of the last four campaigns.
When healthy, he is one of the best hitters in baseball. The three-time All-Star and 2015 American League MVP drilled a combined 78 home runs in 2015 and 2016. His slugging took on even more importance entering the 2017 campaign after Edwin Encarnacion left in free agency.
Darwin Barney started at third base Thursday, with Donaldson listed as the designated hitter. Barney can offer solid glovework in the field but can't replicate Donaldson's impact with the bat.
The Blue Jays will need their slugger back and healthy if they hope to challenge for an American League East title this season.