The dominance of social media (SM) channels in disseminating health-related information during the COVID-19 came with several credibility and reliability issues. Yet, users’ explicit assessment of SM health-related information (SMHI) quality has been less discussed. Situated in Ghana, this study empirically explores the extent to which the source credibility and content reliability influence users’ perception of SMHI quality during the COVID-19 pandemic. Grounded on an integrated SMHI quality evaluation framework, the study hypothesized that the source credibility and content reliability influence users’ perception of SMHI quality. We tested the model using 361 Ghanaian SMHI consumers. The structural equation modeling results indicate that while source credibility influences content reliability, it does not influence users’ perception of quality SMHI during the COVID-19. Again, content reliability significantly influences users’ perceived SMHI quality. We offer several theoretical and practical implications on users’ choice and consumption of health-related information on SM platforms.