Current guidelines recommend high-priority treatment of severe sickle cell disease (SCD) pain with opioids; however, patients with SCD have historically been undertreated. We used mixed methods to assess pediatric residents' perceptions toward opioid use in SCD pain management. We distributed a survey to 88 residents at an urban pediatric medical center in a cross-sectional study. Participants responded to questions about perceived barriers to acute SCD pain management and attitudes toward patients with SCD. Responses were examined using bivariate analyses. Five pediatric residents were interviewed, to provide more in-depth understanding of barriers to SCD pain management. Fifty-three residents (60%) completed the survey. Participants were divided into "more experienced" (had seen ≥ 21 patients with SCD; 45.3%) or "less experienced." Both groups reported potential for tolerance and dependence as major barriers to opioid use in SCD. Less experienced residents reported a greater need for additional training in SCD pain management (P<0.05), more concern about addiction, and greater empathy for patients with SCD (P<0.05). Both groups agreed that patients with SCD were "frustrating to care for." Thematic analysis revealed that increased patient and provider barriers led to distrust, ultimately leading to undertreatment of pain and inadequate care. Although more experienced residents reported feeling more comfortable treating acute SCD pain and were less concerned with addiction compared with less experienced residents, certain negative views of patients with SCD were prevalent among all residents. Findings suggest that residency training must address provider attitudes as well as knowledge about SCD.