Paroxetine is a selective serotonin reuptake inhibitor and one of the most frequently prescribed antidepressants. The serotonin syndrome is a potentially fatal complication of serotonin modifying drugs which is described with clinical triad of mental-status changes, autonomic instability, and neuromuscular abnormalities. Cases determined with therapeutic doses of paroxetine are rare. We present a case of serotonin syndrome presenting with confusion, high fever, rhabdomyolysis, autonomic nervous system dysfunction, acute renal failure and abnormal neuromuscular activity who has needed hospitalization at the intensive care unit after receiving only one tablet [20 mg] of paroxetine and chlorpheniramine 4 mg. We could not find any other serotonin syndrome case report associated with low dose paroxetine and chlorpheniramine use. Physicians need to remain aware of these potential medical complications and integrate this information into their clinical decision-making, informed-consent process, baseline assessment, and follow-up monitoring.