Background: Previous studies have indicated abnormalities in the immune system, such as central nervous system inflammation and high levels of activating cytokines in the cerebrospinal fluid of schizophrenic patients. Celecoxib, a modulator of proinflammatory cytokines, as an adjunctive therapy add-on risperidone (a well-established atypical antipsychotic) and amisulpiride (a benzamide antipsychotic), had improved these patients significantly. Objectives: A trial was conducted to evaluate the therapeutic effects of celecoxib add-on haloperidol, a classic antipsychotic that has been reported to have an immunomodulatory effect and mainly affects positive psychotic symptoms in schizophrenia. Methods: In a prospective, double-blind study, after a washout period, 49 patients with schizophrenia were randomly assigned to either 15 - 30 mg/day haloperidol plus 400 mg/day of celecoxib or the same dose of haloperidol plus placebo for 5 weeks. Psychopathology was evaluated via the Positive and Negative Symptoms Scale (PANSS). The data were reported as mean ± standard deviation and frequency. An Independent t-test was carried out when comparing the data of these two groups for each week. The proportion comparison was carried out using the chi-square test. In terms of age, gender, marital and educational state, and duration or severity of disease or psychopathology and subtypes of schizophrenia, there were no significant differences. Results: Over 5 weeks, there was significantly greater improvement in the celecoxib group in scores on the total PANSS and on positive symptoms and general psychopathology subscales ([t = 2.89, P = 0.006], [t = 2.37, P = 0.022], and [t = 3.34, P = 0.002] respectively). Conclusions: Celecoxib is an efficient adjuvant agent in the treatment of patients with schizophrenia. Significant superiority of management with a modulator of proinflammatory cytokine, which balances immune responses over haloperidol alone, reconfirms the immune dysfunction and inflammation hypothesis of schizophrenia.