The pathophysiology of schizophrenia may involve increased production of inflammatory cytokines by activated microglia. Minocycline can inhibit activated microglia and may improve secondary negative symptoms and/or cognitive functions when used as adjuvant to antipsychotics. Effects on minocycline on primary and enduring negative symptoms in deficit schizophrenia (DS) are unknown. We present a male patient with a 3-year history of DS. He was treated for 12 weeks with risperidone at a maximal dose of 6 mg per day, then for 10 weeks with olanzapine at 20 mg per day. Symptoms did not improve, and body mass index increased from 20.41 to 22.84 kg/m2. Serum levels of several inflammatory cytokines were elevated, so we prescribed minocycline as adjunct to aripiprazole for 12 weeks. Negative symptoms and cognitive impairment improved, and serum levels of inflammatory cytokines decreased. Our case suggests that clinicians may consider minocycline as adjunct therapy to antipsychotics in patients with DS with elevated serum levels of inflammatory cytokines. This highlights the need for further research into possible relationships of minocycline with negative symptoms and cognitive function in patients with DS.