Background: This clinical pharmacy on-call program (CPOP) is a 24-hour, in-house service provided by pharmacy residents. During shifts, challenging situations may arise, which may correlate with depression, anxiety, and stress. Objective: This pilot study aims to describe the implementation of a debriefing program and characterize mental health patterns of residents in the CPOP. Methods: A structured debriefing process was developed to provide support to residents in the CPOP. Over a 1-year period, twelve outgoing pharmacy residents and ten incoming pharmacy residents completed a modified Depression Anxiety Stress Scale (mDASS-21) questionnaire and received a stress perception score (SPS) during debriefing. Data from first and final on-call shifts were compared via a paired Wilcoxon signed-rank test. Residents were referred to an Employee Assistance Program (EAP) based on mDASS-21 and SPS results. Scores from final on-call shifts were compared between residency classes via a Wilcoxon rank sum test. Results: Following successful implementation, 106 debriefing sessions were completed. Pharmacy residents responded to a median number of 38 events per shift. Significant reductions in anxiety and stress scores were observed from the first and final on-call shifts. Six residents were referred to EAP. A lower incidence of depression, anxiety, and stress was observed in pharmacy residents who received debriefing compared to previous residents. Conclusion: The debriefing program provided emotional support to pharmacy residents participating in the CPOP. Implementation of debriefing demonstrated a reduction of anxiety and stress from the beginning to the end of the academic year and in comparison to the previous year.