Rationale:Postoperative intracranial mycoplasma hominis infection was a rare complication. Timely diagnosis was difficult due to its growth characteristics and nonspecific clinical symptoms.Patient concerns:A 52-year-old man underwent bilateral decompressive craniotomy for severe traumatic brain injury. On the seventeenth day after surgery, the patient developed an unexplained high fever. Empirical anti-infective therapy was ineffective, and the fever persisted. In addition, viscous pus oozed from the head incision. Empiric therapy was still ineffective, the fever persisted, and the culture result was negative. The lumbar puncture pressure was 150 mmH2O and the cerebrospinal fluid white blood cell count was 3600 × 106/L, suggesting an intracranial infection.Diagnoses:Culture growth morphologically consistent with mycoplasma species was obtained from multiple specimens (scalp incision fluid and cerebrospinal fluid) and the identification of mycoplasma hominis was confirmed by 16S rDNA sequencing.Intervention:Targeted anti-infective therapy (Minocycline), change of fresh wound dressing, and continued lumbar cerebrospinal fluid drainage.Outcome:At the 3-month follow-up, the patient was still in the rehabilitation department of the local hospital for treatment, but there were no symptoms of intracranial infection.Lessons:Neurosurgeons should carefully examine postoperative incisions and be aware of the possibility of mycoplasma infection during clinical management.