Individuals may show different responses to stressful events. Here, we investigate the neurobiological basis of stress resilience, by showing that neural responsitivity of the noradrenergic locus coeruleus (LC-NE) and associated pupil responses are related to the subsequent change in measures of anxiety and depression in response to prolonged real-life stress. We acquired fMRI and pupillometry data during an emotional-conflict task in medical residents before they underwent stressful emergency-room internships known to be a risk factor for anxiety and depression. The LC-NE conflict response and its functional coupling with the amygdala was associated with stress-related symptom changes in response to the internship. A similar relationship was found for pupil-dilation, a potential marker of LC-NE firing. Our results provide insights into the noradrenergic basis of conflict generation, adaptation and stress resilience.