Background <p>Undergraduate nursing internships are a critical phase in nursing education, where interns often face high levels of perceived stress due to the demands of clinical practice. This stress may contribute to the development of compassion fatigue, which can impair their professional performance and well - being. Resilience, as a psychological resource, has been suggested to buffer the negative effects of stress. However, the mediating role of resilience between perceived stress and compassion fatigue in undergraduate nursing interns remains understudied, highlighting the need for this investigation.</p> Methods <p>A cross - sectional study was conducted using a convenient sampling approach. From January to March 2025, 214 undergraduate nursing interns were recruited from three tertiary grade A general hospitals in Chengdu, China. Data were collected using four validated instruments: a General Information Questionnaire, the Chinese Version of the Compassion Fatigue Short Scale (CF - Short Scale), the Perceived Stress Scale (PSS), and the College Student Resilience Scale. Statistical analyses included descriptive statistics, Pearson correlation analysis, and structural equation modeling (SEM) to examine the mediating effect of resilience. The SEM was used to test the hypothesized model, with maximum likelihood estimation employed.</p> Results <p>Among the 214 undergraduate nursing interns, the mean total scores of compassion fatigue, perceived stress, and resilience were 57.53 ± 31.96, 39.33 ± 13.94, and 102.39 ± 13.94, respectively. Perceived stress was significantly and positively correlated with compassion fatigue (<i>r</i> = 0.289, <i>P</i> &lt; 0.01) and significantly and negatively correlated with resilience (<i>r</i> = − 0.378, <i>P</i> &lt; 0.01). Structural equation modeling showed an acceptable model fit (GFI = 0.842, CFI = 0.896, TLI = 0.854, IFI = 0.897). Perceived stress exerted a significant direct effect on compassion fatigue (standardized β = 0.388, <i>P</i> &lt; 0.001) and a significant indirect effect through resilience (unstandardized indirect effect = − 0.417, 95% CI [− 0.813, − 0.157]). The indirect effect accounted for approximately 23% of the total effect, indicating a partial mediating role of resilience.</p> Conclusions <p>This study demonstrates that resilience plays a partial mediating role in the relationship between perceived stress and compassion fatigue among undergraduate nursing interns. While higher resilience can attenuate the negative impact of perceived stress on compassion fatigue, perceived stress continues to exert a substantial direct effect. These findings indicate that resilience functions as a protective psychological resource but cannot fully offset the harmful effects of stress. Therefore, clinical nursing education programs should adopt dual-focused interventions that both strengthen resilience and prioritize stress management, in order to effectively reduce compassion fatigue and promote the sustainable professional development of nursing interns.</p>