The use of social media has changed since the outbreak of coronavirus disease 2019 (COVID-19). However, little is known about the gender disparity in social media use for nonspecific and health-specific issues before and during the COVID-19 pandemic. Based on a gender difference perspective, this study aimed to examine how the nonspecific and health-specific uses of social media changed in 2017-2020. The data came from the Health Information National Trends Survey Wave 5 Cycle 1-4. This study included 10,426 participants with complete data. Compared to 2017, there were higher levels of general use in 2019 and 2020, and an increased likelihood of health-related use in 2020 was reported among the general population. Female participants were more likely to be nonspecific and health-specific users than males. Moreover, the relationship of gender with general use increased in 2019 and 2020; however, concerning health-related use, it expanded in 2019 but narrowed in 2020. The COVID-19 global pandemic led to increased use of social media, especially for health-related issues among males. These findings further our understanding of the gender gap in health communication through social media, and contribute to targeted messaging to promote health and reduce disparities between different groups during the pandemic.