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Importance: Misinformation about COVID-19 vaccination may contribute substantially to vaccine hesitancy and resistance. Objective: The objective of this survey study is to determine if depressive symptoms are associated with greater likelihood of believing vaccine-related misinformation. Design, Setting, and Participants: This survey study analyzed responses from 2 waves of a 50-state nonprobability internet survey conducted between May and July 2021, in which depressive symptoms were measured using the Patient Health Questionnaire 9-item (PHQ-9). Survey respondents were aged 18 and older. Population-reweighted multiple logistic regression was used to examine the association between moderate or greater depressive symptoms and endorsement of at least 1 item of vaccine misinformation, adjusted for sociodemographic features. The association between depressive symptoms in May and June, and new support for misinformation in the following wave was also examined. Exposures: Depressive symptoms. Main Outcomes and Measures: The main outcome was endorsing any of 4 common vaccine-related statements of misinformation. Results: Among 15,464 survey respondents (9834 [63.6%] women and 5630 [36.4%] men; 722 Asian respondents [4.7%], 1494 Black respondents [9.7%], 1015 Hispanic respondents [6.6%], and 11?863 White respondents [76.7%]; mean [SD] age, 47.9 [17.5] years), 4164 respondents (26.9%) identified moderate or greater depressive symptoms on the PHQ-9, and 2964 respondents (19.2%) endorsed at least 1 vaccine-related statement of misinformation. Presence of depression was associated with increased likelihood of endorsing misinformation (crude odds ratio [OR], 2.33; 95% CI, 2.09-2.61; adjusted OR, 2.15; 95% CI, 1.91-2.43). Respondents endorsing at least 1 misinformation item were significantly less likely to be vaccinated (crude OR, 0.40; 95% CI, 0.36-0.45; adjusted OR, 0.45; 95% CI, 0.40-0.51) and more likely to report vaccine resistance (crude OR, 2.54; 95% CI, 2.21-2.91; adjusted OR, 2.68; 95% CI, 2.89-3.13). Among 2809 respondents who answered a subsequent survey in July, presence of depression in the first survey was associated with greater likelihood of endorsing more misinformation compared with the prior survey (crude OR, 1.98; 95% CI, 1.42-2.75; adjusted OR, 1.63; 95% CI, 1.14-2.33). Conclusions and Relevance: This survey study found that individuals with moderate or greater depressive symptoms were more likely to endorse vaccine-related misinformation, cross-sectionally and at a subsequent survey wave. While this study design cannot address causation, the association between depression and spread and impact of misinformation merits further investigation.