In this case report, we present a 42-year-old man with history of chronic low back pain after a work-related injury. The patient failed multiple therapeutic modalities both conservative and interventional, including numerous spinal injections and placement of a spinal cord stimulator. Finally, an intrathecal morphine pump was placed to control his pain in addition to oral pain medications. The course of the treatment included adding a muscle relaxant, tizanidine (Zanaflex), to control spasms in the lower extremities. Six weeks after starting tizanidine, a large pleural effusion was noted incidentally on a computerized tomography scan of the thoracic and lumbar spine. The patient underwent work-up for the pleural effusion; all tests came back negative. Finally, a drug reaction to tizanidine was suspected. The drug was discontinued, and 4 weeks later the pleural effusion resolved.