Healthcare workers (HCWs) are front-line warriors in the battle against the COVID-19 pandemic. Therefore, it is of interest to assess the psychological and physical effects of personal protective equipment (PPE) among HCWs caring for COVID-19 patients. This cross-sectional study utilized a validated, well-structured questionnaire consisting of 24 questions to collect information on the psychological and physical effects experienced by HCWs. The study adhered to relevant EQUATOR guidelines for reporting. The study collected online data from 114 HCWs working in COVID-19 settings while using PPE. Among the respondents, 33% reported anxiety, 23.1% experienced apprehension after donning PPE, and 68.1% felt discomfort. Additionally, 46.2% required up to 12 hours for psychological restoration after a COVID-19 duty shift, 17.6% were worried about the risk of infection, and 28.6% were extremely worried about infecting family members while on duty. The findings highlight significant discomfort, anxiety, and apprehension among HCWs due to prolonged PPE use, reflecting the immense psychological burden of working in high-risk environments during the pandemic. These results emphasize the need for comprehensive support systems and interventions to address the multifaceted needs of HCWs, including psychological support, adequate breaks, and measures to mitigate physical discomfort.