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The misuse of and addiction to opioids are a national public health crisis. The complexity of delivering patient care in emergency departments exposes nurses to stressful work situations with complex patient loads and increasing levels of compassion fatigue. Emergency nurses were asked about their feelings of compassion fatigue while caring for patients with opioid use and/or substance use disorders.Twenty-four focus groups with emergency nurses (N = 53) at a level I trauma center were conducted in late 2019 and early 2020 are used in this qualitative study using thematic analysis that identified 1 main theme of compassion fatigue with 3 subthemes (nurse frustration with addicted patients, emotional responses, and job satisfaction).Findings highlight that emergency nurses working with patients with opioid use and/or substance use disorders are dealing with a number of negative emotional stressors and frustrations, which in turn has increased their levels of compassion fatigue. These nurses repeatedly expressed feelings of increasing frustration with addicted patients, negative emotional responses, and decreasing levels of job satisfaction as components of their compassion fatigue.These emergency nurses identified 3 areas to improve their compassion: improved management support with encouragement across all work shifts, debriefing opportunities, and more education. Fostering a high level of self-awareness and understanding of how the work environment influences personal well-being are necessary strategies to avoid the frustrations and negative emotional responses associated with compassion fatigue.