Aim <p>Drawing on Conservation of Resources (COR) theory, this research investigates the association between Perceived Organizational Support (POS) and trust in colleagues among nurses, specifically focusing on the mediating effect of emotional exhaustion. Furthermore, it examines how Learning Goal Orientation (LGO) moderates the associations of POS with both emotional exhaustion and trust in colleagues.</p> Background <p>After COVID-19, the healthcare sector has experienced increased emotional exhaustion and an urgent need for trust among nurses. This study explores the interrelationships among POS, emotional exhaustion, and trust in colleagues—an area crucial for team cohesion and patient care quality in high-pressure nursing environments.</p> Methods <p>The study utilized a cross-sectional design with 352 nurse participants. Regression analysis and the PROCESS macro (Version 4.10) were employed to test the proposed relationships, including the mediating role of emotional exhaustion and LGO’s moderating effects.</p> Results <p>Results indicated a positive link between POS and trust in colleagues that is mediated by reduced emotional exhaustion. Regarding moderation, LGO was found to amplify the connections of POS with both emotional exhaustion and trust in colleagues, particularly among nurses exhibiting high LGO.</p> Conclusions <p>These findings highlight the critical role of POS in fostering coworker trust and mitigating emotional exhaustion within the nursing workforce. Enhancing POS can strengthen team dynamics, mitigate the adverse impact of emotional exhaustion, and improve well-being and performance. The results can inform targeted strategies to manage job stress and support nurses with varying levels of LGO.</p> Clinical trial number <p>Not applicable.</p>