Coronavirus disease 2019 (COVID-19) is an emerging infectious disease of pandemic proportions. Healthcare workers in Singapore working in high-risk areas were mandated to wear personal protective equipment (PPE) such as N95 face mask and protective eyewear while attending to patients. We sought to determine the risk factors associated with the development of de novo PPE-associated headaches as well as the perceived impact of these headaches on their personal health and work performance. The impact of COVID-19 on pre-existing headache disorders was also investigated. This is a cross-sectional study among healthcare workers at our tertiary institution who were working in high-risk hospital areas during COVID-19. All respondents completed a self-administered questionnaire. A total of 158 healthcare workers participated in the study. Majority 126/158 (77.8%) were aged 21-35 years. Participants included nurses 102/158 (64.6%), doctors 51/158 (32.3%), and paramedical staff 5/158 (3.2%). Pre-existing primary headache diagnosis was present in about a third 46/158 (29.1%) of respondents. Those based at the emergency department had higher average daily duration of combined PPE exposure compared to those working in isolation wards 7.0 (SD 2.2) vs 5.2 (SD 2.4) hours, P < .0001 or medical ICU 7.0 (SD 2.2) vs 2.2 (SD 0.41) hours, P < .0001. Out of 158 respondents, 128 (81.0%) respondents developed de novo PPE-associated headaches. A pre-existing primary headache diagnosis (OR = 4.20, 95% CI 1.48-15.40; P = .030) and combined PPE usage for >4 hours per day (OR 3.91, 95% CI 1.35-11.31; P = .012) were independently associated with de novo PPE-associated headaches. Since COVID-19 outbreak, 42/46 (91.3%) of respondents with pre-existing headache diagnosis either "agreed" or "strongly agreed" that the increased PPE usage had affected the control of their background headaches, which affected their level of work performance. Most healthcare workers develop de novo PPE-associated headaches or exacerbation of their pre-existing headache disorders.