OBJECTIVE: To determine whether persons with deficit syndrome exhibit lower quality of life than do their counterparts. METHODS: Participants were drawn from the U.S. Schizophrenia Care and Assessment Program (SCAP). Trained assessors collected baseline data. Baseline QLS was used (n = 781; mean = 56) and was modeled as a linear function of covariates, including demographic, clinical, medication adherence, and site variables. Presence of deficit syndrome was assigned based on proxy methods using clinical data collected at the baseline assessment (Kirkpatrick B., et al., 1993). RESULTS: Modeling revealed that deficit syndrome had a negative impact of 4.7 points (p < .001) on quality of life score (range 0–120), suggesting that persons with deficit syndrome may experience a significantly lower quality of life than their non-deficit counterparts, all else equal. Those having higher hallucinations/delusions scores (p < .001) exhibited lower QLS scores and those with higher functioning scores (GAF; p < .001) exhibited higher QLS scores. The presence of insurance other than Medicare or Medicaid (as compared to no insurance) revealed a positive relationship to QLS score. Significance was achieved on one site variable and indicated a negative relationship. Weak evidence was obtained (p = .0587) indicating a positive association between higher education level and QLS score. CONCLUSIONS: Findings suggest that persons with deficit syndrome experience lower quality of life than those who are non-deficit. The result is expected given the use of clinical assessment of quality of life and is contrary to the expectation of higher self-reported quality of life for persons with deficit. Although the clinical and functional scores are significant, the impact of deficit syndrome is at least five times greater than that of hallucinations/delusions. The interpretation of significance on the insurance and site variables is less clear and may suggest that the observed variation is a result of an unobserved mediating process, such as selection or differential access.