The challenge regarding COVID-19 is to prevent complications and fatal evolution. Azithromycin (AZM) and hydroxychloroquine (HCQ) have proven their antiviral effect in vitro. We aimed to assess the efficacy and safety of AZM alone or combined to HCQ, prescribed, at an early stage, in patients with Covid-19, in a primary care setting. Eighty-eight patients received either no or a symptomatic treatment (NST) (n=34) or AZM alone (n=34) or AZM+HCQ (n=20). The efficacy end point was the time to clinical recovery and the safety end point was the occurrence of cardiovascular events. The mean (SD) times to achieve clinical recovery were respectively 25.8 days (11.1), 12.9 days (13.4) and 9.2 days (9.3), showing a statistically significant difference between NST and AZM alone (p<0.0001) or AZM+HCQ (p<0.0001). To improve the evidence level, a case-control analysis was performed on a sample of 57 patients (19/group) matched for age, sex and BMI. The statistical difference between NST and AZM was confirmed (p=0.0149) as well as the difference with AZM+HCQ (p=0.0002). No cardiac toxicity was recorded in any patient. No statistical difference was shown between AZM and AZM+HCQ groups, although the dual therapy tended to be more effective in patients over 50 years, based on an analysis using the cox model. In conclusion, AZM and AZM+HCQ favourably impacted the course of the disease. We need trials, ideally prospective/double blind, to show if a statistical difference can be evidenced with a broader group, and clarify the indications of each treatment depending on initial clinical presentation.