BackgroundSeveral vaccines were introduced in Tanzania to combat the COVID-19 pandemic. While studies have explored the acceptability and hesitancy of COVID-19 vaccines within the general population, there is limited research focusing on the confidence and associated factors among People Living with HIV (PLHIV). This study aims to fill that gap by investigating vaccine confidence and its determinants in this demographic group.MethodsA cross-sectional study was conducted in centres for care and treatment in four regions of mainland Tanzania using structured questionnaires. A generalized linear mixed model was fitted to determine the factors associated with confidence in the COVID-19 vaccine.ResultsA total of 1,100 participants were interviewed; 761 (69.2%) were female. The mean age and standard deviation were 41.6 ±12.1 years. The overall level of confidence in COVID-19 vaccines was 55.3%. Females were less likely to express confidence compared to males (aOR = 0.77; 95% CI: 0.72–0.84). Participants with primary (aOR = 1.79; 95% CI: 1.65–1.94), secondary (aOR = 1.81; 95% CI: 1.57–2.09), and university-level education (aOR = 2.14; 95% CI: 0.17–26.54) were more likely to report confidence in COVID-19 vaccines. Attending a dispensary-level health facility (aOR = 1.32; 95% CI: 1.27–1.38) and living in rural areas (aOR = 1.43; 95% CI: 1.23–1.66) were significantly associated with confidence in COVID-19 vaccines.ConclusionAlthough COVID-19 is no longer a global public threat, these findings highlight the significance of being prepared in public health and the necessity of continuous efforts to comprehend and enhance vaccine acceptance and confidence among people living with HIV. By tackling the factors that impact vaccine attitudes in this group, we can improve our preparedness for future public health challenges where vaccine uptake may once again become crucial.