Objectives <p>As social media platforms like WeChat gain popularity in China, there is a notable lack of research examining the impact of social comparison orientation on users’ mental health. Grounded in the social enhancement hypothesis, this study proposes a hypothetical model to explore the relationship between social comparison orientation (SCO) and social media posting anxiety (SMPA) among WeChat users in China, with fear of missing out (FoMO) serving as a mediator and self-esteem as a moderator.</p> Methods <p>An online survey with 513 Chinese adults who actively use WeChat was conducted from October 9 to November 6, 2022, via a link shared on WeChat. Data analysis was conducted using IBM SPSS Statistics version 23.0. Initially, CFA and Pearson Correlation analyses were conducted for preliminary evaluations. Following this, we performed a mediation analysis utilizing Model 4 and a moderation analysis using Model 1 in SPSS PROCESS.</p> Results <p>The results indicate that individuals with a higher orientation for social comparison are more likely to experience anxiety related to posting on WeChat (B = 0.101, <i>p</i> &lt; .05, 95% CI: [0.006, 0.196]). Furthermore, FoMO partially mediates the relationship between SCO and SMPA (indirect effect = 0.433, 95% CI: [0.356, 0.515]). Importantly, the Johnson-Neyman analysis demonstrates that self-esteem significantly and positively moderates the relationship between SCO and FoMO (all <i>p</i>-values &lt; .001); however, it does not moderate the direct correlation between SCO and SMPA. </p> Conclusions <p>This study supports the social enhancement effect and contributes to a deeper understanding of social media use in China, emphasizing culturally specific nuances. The findings provide theoretical insights for future research and practical recommendations for WeChat users.</p>