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To investigate the mediating role of social network size and perceived quality in the associations of physical activity with quality of life and depressive symptoms in middle-aged and older adults. We analyzed information of 10,569 middle-aged and older adults from waves 2 (2006–2007), 4 (2011–2012), and 6 (2015) of the Survey of Health, Ageing, and Retirement in Europe study (SHARE). Data on physical activity (moderate and vigorous intensities), social network (size and quality), depressive symptoms (EURO-D scale), and quality of life (CASP) were self-reported. Sex, age, country of residency, schooling, occupational status, mobility, and baseline values of the outcome were used as covariates. We created mediation models to test the mediating effect of social network size and quality in the association between physical activity and depressive symptoms. Social network size partly mediated the association between vigorous physical activity and depressive symptoms (7.1%; 95%CI: 1.7–12.6) as well as the association between moderate (9.9%; 1.6–19.7) and vigorous (8.1%; 0.7–15.4) physical activity and quality of life. Social network quality did not mediate any of the associations tested. We conclude that social network's size, but not satisfaction, mediates part of the association of physical activity with depressive symptoms and quality of life in middle-aged and older adults. Future physical activity interventions among middle-aged and older adults should consider increasing social interactions to facilitate benefits for mental health-related outcomes. [ABSTRACT FROM AUTHOR]