Healthcare workers are exposed to a high risk of COVID-19 infection due to close contact with infected patients in healthcare centers. This study aimed to investigate the level of exposure and risk of COVID-19 virus infection among healthcare workers working in primary healthcare centers in Khuzestan province, Iran. This cross-sectional study was conducted among 599 healthcare workers working in primary healthcare centers in the northern region of Khuzestan province, Iran, in 2022. Participants were recruited using a multistage and proportional stratified random sampling method. The WHO COVID-19 risk assessment tool was used to collect data. Data were analyzed using STATA V14.2. The prevalence of occupational and community exposure was 95.7% (93.7 to 97.1) and 89.6% (87.0 to 92.1), respectively. Healthcare workers with occupational exposure had a high risk of exposure (92.7%; 95% CI 90.1 to 94.6). There was no significant association between the type of profession, the role of primary health care workers, and the level of occupational exposure risk (P value > 0.05). The strength of the association was very weak (PR = 1.00; 95% CI 0.94 to 1.07). Also, a significant association was observed between the history of contact with biological materials and adherence to infection prevention and control measures with the level of occupational exposure to the virus (P value < 0.001). The strength of the association between contact with biological materials and exposure risk was weak (aPR = 1.20; 95% CI 1.12 to 1.29), but the strength of the association between adherence to infection prevention and control protocols and exposure risk was strong (aPR = 3.85; 95% CI 2.60 to 5.71). Furthermore, infection prevention and control was identified as a strong confounder in this study. The results showed that the prevalence of occupational exposure was high among healthcare workers, regardless of their profession and roles, with the majority of exposures being of high risk. Primary healthcare managers can play a major role in reducing exposure among high-risk healthcare workers by providing continuous personnel training, investing in the supply chain, prioritizing regular testing and vaccination of HCWs, and ensuring dedicated supervision while accurately monitoring compliance with health protocols during pandemics.