Does bactrim (sulfamethoxazole and trimethoprim) cause indigestion?

Possibly: All medications, including bactrim, (sulfamethoxazole and trimethoprim) can cause symptoms of indigestion. This is primarily due to your intestines being exposed to a medication that it is not "use to." if this is the case, this side effect tends to be temporary. Other medications can cause increased acid irritation to the esophagus. Best to see your doctor if these symptoms persist.