ObjectivesThis study aimed to explore the mediating role of resilience and resignation coping in the relationship between consultation empathy and depression in patients with COVID-19.DesignCross-sectional study.SettingParticipants were recruited from a tertiary hospital in Guangzhou, Guangdong province.ParticipantsA total of 215 patients were recruited for this study.Outcome measuresA total of 215 patients completed the Consultation and Relational Empathy Measure, Connor-Davidson Resilience Scale, Medical Coping Modes Questionnaire and Hospital Anxiety and Depression Scale. PROCESS 4.1 model 6 was used to analyse the moderated mediating effects.ResultsConsultation empathy had a positive correlation with resilience (r=0.34, p<0.001), and a negative correlation with resignation (r=−0.288, p<0.001) and depression (r=−0.379, p<0.001). Resilience had a negative correlation with resignation (r=−0.463, p<0.001) and depression (r=−0.605, p<0.001). Resignation had a positive correlation (r=0.547, p<0.001) with depression. In the moderated mediating model, consultation empathy had significant indirect predictive effects on depression through resilience (95% CI −0.093 to –0.030) or resignation (95% CI −0.043 to –0.005). Consultation empathy had significant indirect predictive effects on depression through both resilience and resignation (95% CI −0.030 to –0.008).ConclusionsConsultation empathy not only predicted depression directly, but also indirectly predicted depression through the chain mediating effects of resilience and resignation coping.