ObjectiveTo describe the drivers of distress and motivations faced by interdisciplinary clinicians who were on the frontline caring for patients with COVID-19.Design50 semistructured interviews. Transcripts were analysed using qualitative thematic analysis.SettingA safety-net hospital in Denver, Colorado.ParticipantsInterdisciplinary frontline clinicians including physicians, advance practice providers, nurses, respiratory therapists and paramedics providing inpatient hospital care to patients hospitalised for COVID-19.ResultsFifty clinicians (32 women and 18 men) participated. Five themes with respective subthemes (in parentheses) were identified: depersonalisation and barriers to care (impeding rapport and compassion, focusing on infection risk at the expense of high-quality care, grief from witnessing patients suffer in isolation), powerless in uncertainty (inescapable awareness of personal risk, therapeutic doubt in a void of evidence, confronting ethical dilemmas, struggling with dynamic and unfamiliar challenges), overwhelmed and exhausted (burden of personal protective equipment (PPE), information overload and confusion, overstretched by additional responsibilities at work, compounded by personal life stressors, feeling vulnerable and dispensable, compassion fatigue, distress from the disproportionate impact on socially oppressed communities), bolstering morale and confidence (motivated by community and family support, equipped with data), and driven by moral duty (responsibility to patient care and community, collegial solidarity and collaboration, contributing to the greater good).ConclusionFrontline clinicians reported distress due to the challenges of PPE, uncertainty and powerlessness, new responsibilities at work and home, losing control of their schedules, grief from witnessing patients suffer in isolation and witnessing healthcare disparities exacerbated by this pandemic. Clinicians feel supported by their colleagues, families, and community and were driven by a sense of moral duty. Healthcare system should adopt strategies to minimise distress faced by interdisciplinary clinicians on the frontline of COVID-19.