Neuropsychological and psychosocial predictors of subjective well-being (SWB) were examined among 74 persons with multiple sclerosis (MS). The multidimensional construct of SWB was assessed by self-report measures of acute psychological distress, global life satisfaction, and health-related quality of life (HRQoL). Objective disease-related indices were obtained from medical records and neuropsychological testing. Unawareness of deficit, a frequent aspect of executive function impairments in MS, was measured as the discrepancy between patient self-report of functional abilities and a caregiver's report of the patient's abilities. Results indicate that a substantial proportion of patients experienced diminished SWB and that disease characteristics such as duration and severity have differential relationships to SWB outcomes. Multiple regression analyses indicated that, in the context of a combined predictive model, social support and unawareness of deficit provided unique information in predicting all three aspects of SWB, beyond that accounted for by disease characteristics. Both social support and unawareness of deficit were associated with positive well-being outcomes. Neuropsychological impairment was adversely related to life satisfaction and HRQoL, but it did not add unique information to the prediction of these outcomes. The findings present a unique view of SWB among individuals with MS in the absence of acute exacerbation of the illness.