Officers first responded around 12 a.m. on Wednesday to a medical event in the east end of the city.
Police members administered doses of naloxone as a result of the man being in cardiac arrest due to a suspected drug overdose and did CPR until EMS arrived and took over medical care.
The efforts of police and EMS were unsuccessful and he was pronounced dead, according to a press release.
Another call during the late evening hours of Wednesday reporting a man in medical distress just outside the west edge of city limits. He was taken to Weyburn General Hospital but did not survive, police said.
The third suspected overdose was reported in the city at 1 p.m. on Thursday. During this call, police said the man found unconscious was revived after being administered Narcan by a responding officer as well as being treated by EMS personnel.
Weyburn is approximately 105 km southeast of Regina.