Patients with a new cancer diagnosis can experience distress when diagnosed. There are disparities in treatment of cancer patients based on social determinants, but minimal research exists on the relationship of those social determinants and distress after a new cancer diagnosis. Our goals were to determine the social determinants associated with distress after a new cancer diagnosis and determine the relationship of distress with outcome. Patients with a new cancer diagnosis at one institution from January 2019 to December 2020 were analyzed. Patients were given the National Comprehensive Cancer Network (NCCN) distress thermometer during their first visit. Demographics, tumor characteristics, clinical variables and survival were recorded. Patients were also asked to share specific factors that led to distress, including: (1) financial, (2) transportation, (3) childcare and (4) religious. A total of 916 patients returned distress thermometers. Mean age was 59.1 years. Females comprised 71.3 (653/916) percent of the cohort. On Dunn’s multiple comparison, the following factors were associated with increased distress level: female (p < 0.01), ages 27 to 45 (p < 0.01), uninsured (p < 0.01) and unemployed (p < 0.01). Patients with higher distress scores also experienced worse overall survival (p < 0.05). Females, young patients, uninsured patients and unemployed patients experience more distress after a new cancer diagnosis. Increased distress is independently associated with worse overall survival. Social determinants can be used to predict which patients may require focused interventions to reduce distress after a new cancer diagnosis.