Improving the psychological well-being of individuals with osteoarthritis (OA) is an important concern because the condition is highly prevalent and has no known cure. Few studies have assessed the joint contribution of social, personality, and physical factors in relation to well-being for OA patients. In a cross-sectional sample of older adults with OA (n = 73, 73% female), we assessed the role of support perceptions, optimism and pain in depressive symptoms and life satisfaction. Greater optimism and support were significantly related to both greater life satisfaction and lower depressive symptoms. Further, optimism partially mediated the relationship of pain to life satisfaction, while support partially mediated the role of pain in depressive symptoms. The interplay of these variables in relation to well-being is discussed in the context of chronic illness and older adulthood.