Juvenile fibromyalgia (JFM) is a chronic pain syndrome affecting mainly adolescent females that is often accompanied by affective symptoms. Resilience may be a protective factor in coping with pain and its impact, reducing affective burden, and promoting a positive outlook in JFM. This study aimed to investigate, for the first time, the differences between high-resilience and low-resilience JFM adolescents on core disease symptoms, affective symptoms, and brain functional connectivity measures. The study included 41 adolescent females with JFM and 40 matched pain-free adolescent females who underwent a resting-state fMRI exam and completed validated questionnaires. Based on patients’ Shift-and-Persist scores, the researchers performed a hierarchical clustering analysis in the JFM group and assessed clinical and connectivity differences between the two resulting clusters of patients (high vs. low resilience). The results showed that the low resilience group experienced more severe affective symptoms and less ability to effectively cope with pain than the high resilience group. The high resilience group showed significantly stronger connectivity in areas of the default-mode network involved in self-related processing and mentalizing.