This pilot study examined the effect of adjunctive salsalate on psychopathology and cognition in patients with schizophrenia. This was a 12-week, open-label trial of salsalate (1.5 g, twice per day) in patients with schizophrenia. Psychopathology, cognition, and daily function were assessed at baseline and week 12 using various rating scales. Blood levels of inflammatory markers including white blood cell count, high-sensitivity C-reactive protein, and interleukin-6 levels were also measured. Eight patients completed the study. There was no significant change in any of the rating scales at week 12. However, there was a trend decrease in the Positive and Negative Syndrome Scale total score, and a trend improvement in the Brief University of California San Diego Performance-based Skills Assessment total score (58.3 +/- 11.4 vs. 53.5 +/- 11.9, P=0.072; 69.7 +/- 18.2 vs. 79.1 +/- 15.9, P = 0.084, respectively). There was a trend improvement in quality of life as measured by the Quality of Life Scale total score (74.0 +/- 20.8 vs. 76.9 +/- 22.7, P = 0.080). There was a significant decrease in white blood cell count (6.8 +/- 1.3 vs. 6.0 +/- 1.2 k/mm(3), P = 0.022). There was no change in the levels of high-sensitivity C-reactive protein or interleukin-6 over 12 weeks (P's > 0.1). Salsalate may have positive therapeutic effect in patients with schizophrenia. Future studies to examine potential benefits of salsalate as an adjunctive treatment to improve clinical symptoms and daily function in patients with schizophrenia are warranted. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.