BACKGROUND Chronic subdural effusion is very common in the cranial imaging of middle-aged and older people. Herein, we report a patient misdiagnosed with subdural effusion, who was eventually diagnosed with chronic subdural empyema (SDE) caused by Streptococcus pneumoniae. CASE SUMMARY A 63-year-old man was brought to our emergency room with a headache, vomiting, and disturbed consciousness. Computed tomography (CT) revealed a bilateral subdural effusion at the top left side of the frontal lobe. Cerebrospinal fluid examination after lumbar puncture indicated suppurative meningitis, which improved after anti-infective therapy. However, the patient then presented with acute cognitive dysfunction and right limb paralysis. Repeat CT showed an increase in left frontoparietal subdural effusion, disappearance of the left lateral ventricle, and a shift of the midline to the right. Urgent burr hole drainage showed SDE that was culture-positive for Streptococcus pneumoniae. His condition improved after adequate drainage and antibiotic treatment. CONCLUSION Patients with unexplained subdural effusion, especially asymmetric subdural effusion with intracranial infection, should be assessed for chronic SDE. Early surgical treatment may be beneficial.