ObjectiveTo assess the perceived social support and professional quality of life (ProQOL) among healthcare professionals during COVID-19 pandemic in Nepal, encompassing both positive (compassion satisfaction) and negative (compassion fatigue) dimensions as well as the factors associated with them.DesignA cross-sectional web-based study.SettingNepalParticipantsWe carried out a convenience sampling technique to enrol 313 health professionals aged 18–60 years old.Outcome measuresWe employed the ProQOL V.5 questionnaire (comparing 30 self-report items) and the Multidimensional Scale of Perceived Social Support with 12 items to assess the ProQOL and social support, respectively. A χ2test was performed to determine associated factors of different dimensions of ProQOL.ResultsThe study included a total of 313 participants, mostly consisting of frontline health workers. More than one-third of the participants worked in places where precautionary measures were insufficient. However, the majority of them (73.8%) had high social support. Concerning the ProQOL, the percentage of health professionals that had moderate compassion satisfaction (CS), moderate Burnout (BO) and moderate secondary traumatic stress (STS) were 57.5%, 58.2% and 75.4%, respectively. Factors like sex, marital status, profession, work-shift, type of health institution and status of precautionary measures at the workplace were associated with the different dimensions of ProQOL at the significance level of 0.05.ConclusionThis study findings revealed a considerable proportion of BO and STS among health professionals during COVID-19 pandemic in Nepal. Implementation of appropriate interventions and support systems are needed to enhance CS, alleviate BO and mitigate STS among health professionals to combat future health emergencies.