People experiencing homelessness (PEH) are at high risk for COVID-19 complications and fatality, and have been prioritized for vaccination in many areas. Yet little is known about vaccine acceptance in this population. The objective of this study was to determine the level of vaccine hesitancy among PEH in Los Angeles, CA and to understand the covariates of hesitancy in relation to COVID-19 risk, threat perception, self-protection and information sources. A novel mobile survey platform was deployed to recruit PEH from a federally qualified health center (FQHC) in Los Angeles to participate in a monthly rapid response study of COVID-19 attitudes, behaviors, and risks. Of 90 PEH surveyed, 43 (48%) expressed some level of vaccine hesitancy based either on actual vaccine offers (17/90 = 19%) or a hypothetical offer (73/90 = 81%). In bivariate analysis, those with high COVID-19 threat perception were less likely to be vaccine hesitant (OR = 0.34, P = 0.03), while those who frequently practiced COVID-19 protective behaviors were more likely to be vaccine hesitant (OR = 2.21, P = 0.08). In a multivariate model, those with high threat perception (AOR = 0.25, P = 0.02) were less likely to be hesitant, while those engaging in COVID-19 protective behaviors were more hesitant (AOR = 3.63, P = 0.02). Those who trusted official sources were less hesitant (AOR = 0.37, P = 0.08) while those who trusted friends and family for COVID-19 information (AOR = 2.70, P = 0.07) were more likely to be hesitant. Findings suggest that targeted educational and social influence interventions are needed to address high levels of vaccine hesitancy among PEH.