The COVID-19 pandemic represents a public health challenge for health systems in the developing world. The objective of this study was to assess, among healthcare professionals in Guinea, the factors associated with COVID-19 perceived susceptibility and severity. We conducted a cross-sectional study in April 2020 among 1058 healthcare professionals as part of the rapid assessment of the Guinean health system preparedness and response to the COVID-19 pandemic. The median level of perceived susceptibility to COVID-19 among healthcare professionals was 6 (IQR: 6-10). About 74.57% of participants said that the COVID-19 was more severe in the elderly than in other age groups. Overall, 41.97% of participants said that healthcare professionals were more prone to get COVID-19 than other professionals, and 67.58% said that the risk of contracting COVID-19 in healthcare facilities was higher than anywhere else. Being a woman (β=0.37 [0.02; 0.73]), an allied healthcare professional (β=0.64 [0.23; 1.06]), perceiving the elderly as more likely to contract COVID-19 (β=0.48 [0.11; 0.86]) and accepting the closure of places of worship (β=0.47 [0.00; 0.93]) were predictors of higher perceived level of susceptibility to COVID-19. The level of perceived susceptibility to COVID-19 was very high among health professionals in the early stages of the COVID-19 pandemic in Guinea. Strategies to empower and improve health professionals' knowledge are needed to balance their provision of good quality care to patients with their responsibility and ability to protect themselves and their families.