Objectives Recent research has focused on the inflammatory cascade as a key culprit in the etiology of bipolar disorder. We hypothesized that celecoxib, via its anti-inflammatory properties, may have a therapeutic role in mood disorder. Methods Forty-six inpatients with the diagnosis of acute bipolar mania without psychotic features participated in a parallel, randomized, double-blind, placebo-controlled trial, and underwent six weeks of treatment with either celecoxib (400 mg daily) or placebo as an adjunctive treatment to sodium valproate. Patients were evaluated using the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS). The primary outcome measure with respect to efficacy was the mean decrease in YMRS score from baseline to the study endpoint, which was compared between the two groups. Results A significant difference was observed in the change in YMRS scores on Day 42 compared to baseline in the two groups (p