Background: The aim of this study was to investigate the diagnostic accuracy of symptoms and signs in healthcare workers (HCW) with Sars-CoV-2. Methods: This was a case-control study. Cases consisted of symptomatic healthcare workers who had a positive SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) test, while controls were symptomatic healthcare workers with a negative RT-PCR test. For each symptom, ROCs were plotted. Diagnostic accuracy was calculated using the sensitivity, specificity, and positive and negative predictive values. A logistic regression analysis was carried out for calculating the OR (95% CI) for each symptom associated to the SARS-CoV-2 positivity. Results: We recruited 30 cases and 75 controls. Fever had the best sensitivity while dyspnea, anosmia, and ageusia had the highest specificity. The highest PPVs were found again for dyspnea (75%), anosmia (73.7%), and ageusia (66.7%). Lastly, the highest NPVs were related to anosmia (81.4%) and ageusia (79.3%). Anosmia (OR = 14.75; 95% CI: 4.27–50.87), ageusia (OR = 9.18; 95% CI: 2.80–30.15), and headache (OR = 3.92; 95% CI: 1.45–10.56) are significantly associated to SARS-CoV-2 positivity. Conclusions: Anosmia and ageusia should be considered in addition to the well-established fever, cough, and dyspnea. In a resource-limited setting, this method could save time and money.