Background: Coronavirus disease 2019 (COVID-19) has attracted global attention as it has expeditiously spread. Therefore, adherence to Personal Protective Equipment (PPE) has become a daily necessity, particularly among front-line personnel. However, PPE is associated with some adverse skin reactions; hence, this study aimed to investigate the characteristics and prevalence of adverse skin reactions from PPE usage. Methods: This cross-sectional study with a random sample was carried out at Bahrain Defense Force Hospital (BDF) from January to March 2021, targeting the front-line personnel. An online questionnaire was sent regarding adverse skin reactions from PPE. A total of 145 healthcare workers (HCWs) were approached, and 132 (91%) responded. The results were analyzed through SPSS 21.0 software, and the Chi-square test or Fisher’s exact test was used to analyze discrete variables. Results: A total of 100 (75.8%) respondents suffered from adverse skin reactions. The most common findings were skin dryness, 100 (75.8%); itchiness, 67 (50.8%); and acne, 48 (36.4%). The most affected distant site was hands, 92 (69.7%). Female gender was significantly associated with skin changes, and only 22 (22%) participants with adverse skin reactions took medical advice. Conclusion: Adverse skin reactions from PPE were common. Therefore, improving awareness of practical methods is quintessential. Keywords: COVID-19; Eczema; Hand Hygiene; Masks; Skin Care