BACKGROUND: Despite the benefits of physical activity for individuals with knee osteoarthritis (KOA), physical activity levels are low in this population. OBJECTIVES: We conducted a repeated cross-sectional study to compare mindset about physical activity among individuals with and without KOA and to investigate whether mindset relates to physical activity. METHODS: Participants with (n = 150) and without (n = 152) KOA completed an online survey at enrollment (T1). Participants with KOA repeated the survey 3 weeks later (T2; n = 62). The mindset questionnaire, scored from 1 to 4, assessed the extent to which individuals associate the process of exercising with less appeal-focused qualities (e.g., boring, painful, isolating, and depriving) versus appeal-focused (e.g., fun, pleasurable, social, and indulgent). Using linear regression, we examined the relationship between mindset and having KOA, and, in the subgroup of KOA participants, the relationship between mindset at T1 and self-reported physical activity at T2. We also compared mindset between people who use medication for management and those who use exercise. RESULTS: Within the KOA group, a more appeal-focused mindset was associated with higher future physical activity (ß=38.72, p = 0.006) when controlling for demographics, health, and KOA symptoms. Individuals who used exercise with or without pain medication or injections had a more appeal-focused mindset than those who used medication or injections without exercise (p<0.001). A less appeal-focused mindset regarding physical activity was not significantly associated with KOA (ß = -0.14, p = 0.067). Further, the mindset score demonstrated strong internal consistency (α = 0.92; T1; n = 150 and α = 0.92; T2; n = 62) and test-retest reliability (intraclass correlation coefficient (ICC) > 0.84, p < 0.001) within the KOA sample. CONCLUSIONS: In individuals with KOA, mindset is associated with future physical activity levels and relates to the individual's management strategy. Mindset is a reliable and malleable construct and may be a valuable target for increasing physical activity and improving adherence to rehabilitation strategies involving exercise among individuals with KOA.