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Prior studies indicated that actively using social network sites (SNSs) is positively associated with well-being by enhancing social support and feelings of connectedness. Conversely, passively using SNSs is negatively associated with well-being by fostering upward social comparison and envy. However, the majority of these studies has focused on Facebook. The present research examined the relationships between well-being-satisfaction with life, negative affect, positive affect-and using actively or passively various SNSs-Facebook, Instagram, Twitter, TikTok-during the COVID-19 pandemic. In addition, two mediators were tested: social support and upward social comparison. One thousand four persons completed an online survey during the quarantine measures; the analyses employed structural equation modeling. Results showed that passive usage of Facebook is negatively related to well-being through upward social comparison, whereas active usage of Instagram is positively related to satisfaction with life and negative affect through social support. Furthermore, active usage of Twitter was positively related to satisfaction with life through social support; while passive usage was negatively related to upward social comparison, which, in turn, was associated with more negative affect. Finally, TikTok use was not associated with well-being. Results are discussed in line with SNSs' architectures and users' motivations. Future research is required to go beyond methodological and statistical limitations and allow generalization. This study concludes that SNSs must be differentiated to truly understand how they shape human interactions.