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People with bipolar disorders report a lower quality of life than the general population does, and few mutable factors associated with health-related quality of life (HRQoL) among people with bipolar disorders have been identified. Using a cross-sectional design, these analyses examined whether self-efficacy was associated with mental and physical HRQoL in a sample of 141 patients with bipolar disorder who completed baseline assessments for two randomized controlled trials. Multiple linear regression analyses indicated that higher levels of self-efficacy were associated with higher mental and physical HRQoL, after controlling for demographic factors and clinical factors (including mood symptoms, comorbid medical conditions, and substance use). Future research should examine whether targeted treatments that aim to improve self-efficacy (such as self-management interventions) lead to improvements in HRQoL among people with bipolar disorder and other serious mental illnesses.