Background People's lives were seriously affected by the emergence and the spread of the COVID-19 disease. Several vaccines were developed in record time to overcome this pandemic. However, putting an end to this public health problem requires substantial vaccination coverage rate. This latter depends on the acceptance of these vaccines especially by health professionals; the leaders of the current war against COVID-19. In fact, they have a central role in promoting vaccination against the SARS-CoV-2. In the developed countries, hesitancy rates towards these vaccines among health professionals vary from 4.3% to 72%. In the developing countries, few studies focused on this issue. Objective To estimate the prevalence and the predictors of SARS-CoV-2 vaccine hesitancy among the Tunisian health professionals. Methods A cross-sectional study was led online between the 7th and the 21th of January 2021 among Tunisian health professionals. At least 460 participants were required. Snowball sampling method served to recruit participants. Data were collected using a pre-established and pre-tested questionnaire recorded in a free Google form. The link of the questionnaire was disseminated online to be self-administered anonymously to the participants. The generated online Google Sheet was uploaded and exported to SPSS software for analysis. Results Of the 546 responses, 493 were retained. The mean age of participants was 37.4 (± 9.5) years. Females represented 70.2% of participants. Social media represented the most frequently used source of information about COVID-19. The prevalence of SARS-CoV-2 vaccine hesitancy among participants was 51.9% (95% CI: 47.5–56.3)). Female sex, working far from the capital and having concerns about the vaccines components predicted more hesitancy among participants. In contrast, the use of the national COVID-19 information website predicted less hesitancy among them. Conclusions The current Tunisian communication plan about COVID-19 vaccines must be reinforced. Social media represent a cost effective communication channel that can serve to reassure Tunisian health professionals regarding the safety of COVID-19 vaccines. Special interest should be paid to females, paramedical professionals and those working far from the capital.