This is a 12-week, open-label trial of salsalate 3 g/day as an adjunctive treatment in 15 schizophrenia subjects to examine salsalate's effect on psychopathology, cognitive functioning, and metabolic parameters.

Potential subjects will be identified by their clinicians at the Freedom Trail Clinic, or Massachusetts General Hospital. A total of 15 subjects will be enrolled.

The specific aims include:

Primary aims:

1. Examine the efficacy of salsalate (3g/day) in improving positive and negative symptoms as measured by the Positive and Negative Syndrome Scale (PANSS) and the Scale for Assessment of Negative Symptoms (SANS).
2. Examine the efficacy of salsalate in improving cognition as measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) composite score.

Secondary aims:

1. Examine salsalate's effects on inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), TNF-α and IL-6.

Inclusion Criteria:

• Age 18-65 years;
• Diagnosis of schizophrenia or schizoaffective disorder;
• Stable dose of the current antipsychotic drug for at least one month;
• Well established compliance with outpatient treatment per treating clinician's judgment;
• Able to complete the cognitive assessment battery (must be English speaking);
• Female subjects will be eligible to participate in the study if they are of non-childbearing potential or of child-bearing potential and willing to practice appropriate birth control methods during the study.

Exclusion Criteria:

• Inability to provide informed consent;
• Current substance abuse;
• Psychiatrically unstable per treating clinician's judgment;
• Significant medical illnesses including uncontrolled hypertension, diabetes, seizure disorder, severe cardiovascular, cerebrovascular, pulmonary, or thyroid diseases;
• Currently on immunosuppressant medication including oral steroids;
• Use of anti-coagulants (heparin, LMWH, warfarin, cilostazol, clopidogrel, dabigatran);
• History of chronic infection (including, HIV and hepatitis), malignancy, organ transplantation, blood dyscrasia, central nervous system demyelinating disorder, and any other known autoimmune or inflammatory condition;
• Experienced asthma, urticaria or allergic type reaction after taking aspirin, salsalate, or other NSAIDS;
• Pregnancy or breastfeeding;
• Pre-existing chronic tinnitus.
• Known hypersensitivity to salsalate.