Since the emergence of COVID-19, several different medicines including antimicrobials have been administered to patients to treat COVID-19. This is despite limited evidence of the effectiveness of many of these, fueled by misinformation. These utilization patterns have resulted in concerns for patients’ safety and a rise in antimicrobial resistance (AMR). Healthcare workers (HCWs) were required to serve in high-risk areas throughout the pandemic. Consequently, they may be inclined towards self-medication. However, they have a responsibility to ensure any medicines recommended or prescribed for the management of patients with COVID-19 are evidence-based. However, this is not always the case. A descriptive cross-sectional study was conducted among HCWs in six districts of the Punjab to assess their knowledge, attitude and practices of self-medication during the ongoing pandemic. This included HCWs working a range of public sector hospitals in the Punjab Province. A total of 1173 HCWs were included in the final analysis. The majority of HCWs possessed good knowledge regarding self-medication and good attitudes. However, 60% were practicing self-medication amid the COVID-19 pandemic. The most frequent medicines consumed by the HCWs under self-medication were antipyretics (100%), antibiotics (80.4%) and vitamins (59.9%). Azithromycin was the most commonly purchase antibiotic (35.1%). In conclusion, HCWs possess good knowledge of, and attitude regarding, medicines they purchased. However, there are concerns that high rates of purchasing antibiotics, especially “Watch” antibiotics, for self-medication may enhance AMR. This needs addressing.