The COVID-19 pandemic poses substantial risks to individuals’ physical and mental health and prolonged psychological responses to the pandemic could lead to emotional exhaustion. The present study aimed to examine the mediating role of COVID-19 related mental impact and distress in the relationship among resilience, burnout, and well-being. The present study recruited 500 community adults (mean age = 38.8 years, SD = 13.9; 76% females) in Hong Kong via an online survey in autumn 2021. The participants completed the Mental Impact and Distress Scale: COVID-19 (MIDc) and validated measures on resilience, burnout, and well-being. Confirmatory factor analysis was conducted to evaluate the psychometric properties of the MIDc. Direct and indirect effects of resilience on burnout and well-being via MIDc were examined via structural equation modeling. Confirmatory factor analysis supported factorial validity for the three factors of MIDc (situational impact, anticipation, and modulation). Resilience showed negative effects on the MIDc (β = −0.69, SE = 0.04, p < 0.01) and burnout (β = 0.23, SE = 0.06, p < 0.01). Burnout was positively associated with MIDc (β = 0.63, SE = 0.06, p < 0.01) and negatively associated with well-being (β = −0.47, SE = 0.07, p < 0.01). Resilience showed a significant and positive indirect effect (αβγ = 0.203, 95% CI = 0.131 to 0.285) on well-being via MIDc and burnout. The results support a potential mediating role for MIDc as psychological responses in the relationship among resilience and burnout and well-being.