Santos has been on the disabled list with inflammation in his shoulder since April 21. He was originally expected to be out for only two to four weeks, but more than two months have passed and he still hasn't experienced any improvement.
Toronto's Opening Day closer has started throwing and stopped on at least a couple of occasions and has been unable to take part in loss toss because of the lingering soreness.
"It has been frustrating for him, because as he has increased the intensity, got back to the mound, had the setback," manager John Farrell said. "I think if you ask any athlete when they have a setback because of an injury, it's frustrating. Then you follow up with further evaluation, the images that take place to get further information.
"We're all hopeful that there's not another setback, because at that point then we've got to really re-assess what the next step is."
Perhaps the most bizarre aspect of Santos' injury woes is that the pain hasn't been restricted to one area of the shoulder.
"He has experienced discomfort on the front side, he has experienced it on the back side," Farrell said. "It has moved around at times and that's -- without speaking directly for Sergio -- I think where some of the frustration lies, because it's not always in one same spot."
Santos appeared in just six games for the Blue Jays this season before going on the DL. Last year with the White Sox, Santos was 4-5 with 30 saves and a 3.55 ERA in 63 1/3 innings.