Background <p>Duloxetine is a serotonin-norepinephrine reuptake inhibitor commonly used to treat depression and neuropathic pain. Duloxetine-associated parkinsonism has been previously reported in only two cases with psychiatric disorders. We present the first case where duloxetine unmasked motor manifestations of subclinical Parkinson’s disease.</p> Case presentation <p>A 41-year-old male underwent a discectomy for a lumbar herniation. As numbness in the left sole persisted postoperatively, duloxetine (20 mg/day) was initiated seven days after surgery. Two days&#xa0;later, the patient developed a slow gait, difficulty turning, and short steps. Neurological examination revealed resting tremor in the left foot, dystonic posturing of the left little toe, bradykinesia of both hands, reduced gait speed with short steps, and rigidity in the left lower limb and neck. Based on the temporal association, duloxetine-associated parkinsonism was suspected. Four days after discontinuing duloxetine, the patient's gait speed, step length, and right-hand bradykinesia improved, and the foot tremor and toe dystonia resolved. Dopamine transporter single-photon emission computed tomography revealed reduced tracer uptake in the bilateral striatum, leading to a diagnosis of duloxetine-associated parkinsonism and subclinical Parkinson’s disease. One year and four months later, gait impairment reappeared, characterized by short steps and slow speed, though without foot tremor or toe dystonia.</p> Conclusion <p>In this case, duloxetine appeared to unmask parkinsonism associated with subclinical Parkinson’s disease. Potential mechanisms include inhibition of dopamine release due to 5-HT₂ receptor activation, postoperative effects, drug hypersensitivity, or genetic phenotypes in serotonin receptors. This case highlights the importance of considering subclinical Parkinson’s disease in patients with duloxetine-associated parkinsonism.</p>