Objectives: The aim of the study was to evaluate the clinical presentation and burden of SARS-CoV-2 infections among medical school physicians and residents, mainly young medical doctors. The awareness of COVID‑19 clinical manifestations can improve the early detection of mild cases, possibly reducing further transmission to colleagues and patients. Material and Methods: The study was carried out in March–May 2020, involving medical school physicians in a teaching hospital in northern Italy, with a working population of 881 medical doctors. Data collection was performed using a structured form investigating clinical and epidemiological information. Results: One hundred sixty-two medical doctors contacted the Occupational Health Service reporting acute respiratory symptoms or close contact exposure to a confirmed COVID‑19 case. Among the confirmed COVID‑19 cases, most were male doctors during residency, and 85% presented a mild clinical picture. Fever (70.3%) and cough (51.4%) represented the most prevalent symptoms of COVID‑19. As revealed by the univariate analysis, the prevalence of real-time reverse transcriptase-polymerase chain reaction (RT-PCR) positivity increased with age (OR = 1.08, 95% CI: 1.02–1.14, p = 0.012), working in a COVID‑19 ward (OR = 3.33, 95% CI: 1.09–10.21, p = 0.031), presenting alteration or loss of smell/taste (OR = 10.00, 95%CI: 2.80–35.69, p < 0.001) and myalgia (OR = 3.20, 95% CI: 1.00–10.26, p = 0.046), while being a resident (OR = 0.20, 95% CI: 0.05–0.80, p = 0.030) was associated with reduced odds of being infected, compared to staff physicians. Age and loss of smell/taste were the only factors independently associated with RT-PCR positivity. Conclusions: The majority of COVID‑19 cases showed a mild clinical syndrome, ranging from absence or paucity of symptoms to common cold or influenza-like symptoms. The findings of the present study increase the accuracy of the clinical diagnosis for the prompt identification and management of suspected COVID‑19 cases, being particularly useful during resurges of the SARS-CoV-2 pandemic. Int J Occup Med Environ Health. 2021;34(2):189–201