Background: Healthcare workers are vulnerable to burnout, especially during the COVID-19 pandemic in the low resource settings. Belize is a small Central American developing country known for its chronic healthcare worker shortage and this is the first study to assess burnout prevalence and its associated factors among healthcare workers in Belize. Aim: To evaluate the prevalence of burnout and its associated factors in HCWs in Belize covering multiple domains (mental health, physical symptoms, and coping behaviors) during the COVID-19 pandemic. Methods: A cross-sectional survey that was developed and validated by a panel of experts was delivered online to all the healthcare workers in Belize from September to November 2021. Burnout was assessed using Copenhagen Burnout Inventory. Depression and anxiety screening was carried out using the Patient Health Questionnaire – 2 (PHQ-2) and Generalized Anxiety Disorder 2-item (GAD-2). Burnout associated factors were estimated using logistic regression models. Findings: Of the total of 263 participants, 27.76% had overall burnout: 56.65% had personal, 54.37% had work-related, and 19.39% had patient-related burnout. Burnout was positively associated with anxiety (OR: 3.14 [1.67, 5.92]), depression (OR: 4.45 [2.30, 8.61]), intentions of quitting their jobs (OR: 2.59 [1.49, 4.51]), health status worsening (OR: 2.21 [1.26, 3.87]), multiple physical symptom presentation (OR: 1.19, [1.10, 1.29]), and use of multiple maladaptive coping behaviors (OR: 1.66, [1.30, 2.12]). Interpretation: Healthcare workers in Belize showed substantial levels of burnout which were significantly associated with using maladaptive coping behaviors, presenting multiple physical symptoms, quitting their jobs, health status worsening, and other mental health issues. These findings should be used to develop and implement programs such as regular health check-ups, health promotion awareness campaigns, and worker recruitment strategies which would improve the working conditions, quality of life, and psychological well-being of our healthcare workers.