The COVID-19 pandemic has highlighted the importance of healthcare workers and their professional quality of life. This quantitative cross-sectional study aims at exploring the professional quality of life, work engagement, and self-care of healthcare workers during the COVID-19 pandemic in Ecuador. A convenience sample of 117 participants completed an online voluntary and anonymous survey between April and July 2020. It contained a sociodemographic section, the Professional Quality of Life questionnaire V, the work engagement scale, and the scale of self-care behaviors for clinical psychologists. Results show that healthcare workers have an average quality of life with high levels of compassion satisfaction and average levels of compassion fatigue and burnout. Data also indicate that the sample frequently engaged in self-care practices and had high levels of work engagement. The regression analyses reveal that gender, the number of patients per week, the perceived fairness of the salary, among other variables are possible predictors of professional quality of life, frequency of self-care practices, and engagement. This study contributes to the understanding of these variables among healthcare professionals in Ecuador. These results should be considered when planning policies and prevention intervention efforts to promote professionals’ wellbeing.