Cancer is the leading cause of death in Puerto Rico (PR). Hurricane Maria (HM) and its aftermath lead to widespread devastation in the island, including the collapse of the healthcare system. Medically fragile populations, such as cancer survivors, were significantly affected. The goal of this study was to assess the impact of HM on barriers to care, emotional distress, and inflammatory biomarkers among cancer survivors in PR. This exploratory longitudinal study was conducted in health care facilities and community support groups from PR. Cancer survivors (n=50) and non-cancer participants (n=50) completed psychosocial questionnaires and provided blood samples that were used to assess inflammatory cytokines levels. Data were analyzed through descriptive, frequencies, correlational, and linear regression analyses. Cancer survivors that were affected by HM reported increased barriers in accessing medical care, which were directly associated with anxiety, perceived stress, and post-traumatic symptomatology. Moreover, being a cancer survivor, along with closeness in time from HM predicted more barriers to receiving health care. Several inflammatory cytokines, such as CD31, BDNF, TFF3, Serpin E-1, Vitamin D BP, VCAM-1, Osteopontin, Chitinase 3 like 1, MMP-9 and MIF were significantly upregulated in cancer survivors while BDNF, MMP9 and Osteopontin had significant positive correlations with barriers to care. HM significantly impacted Puerto Ricans psychosocial well-being. Cancer survivors had significant barriers to care and showed increased serum inflammatory cytokines, but did not show differences in anxiety, stress and post-traumatic symptoms compared to non-cancer participants