Background: Mental distress is associated with poor treatment adherence and adverse psychosocial outcomes, and cancer survivors, especially adolescent and young adults (AYA), may experience greater distress than older adults and the general population. We tested this hypothesis by examining the association between AYA vs. adult cancer survivors vs. the general population without a history of cancer, and mental distress. Methods: Using the 2014-2017 National Health Interview Surveys, 2,516 AYA cancer survivors (aged 15 – 39 years) were identified. We then used propensity score matching (matched on sociodemographics, comorbidities, smoking status and visit to mental health professional in past year) to create 2,516 older cancer survivors (aged ≥ 40 years); and 2,516 adults without cancer (general population) as the comparison groups. Mental distress (outcome of interest) was measured using the validated Kessler nonspecific mental/psychological distress (K6) scale. The 6-item K6 scale examines how frequently within the past 30 days an individual felt nervous, hopeless, restless or fidgety, worthless, sad, and that everything was an effort. Responses were summed to yield a score ranging between 0 and 24 and classified as none/low (0≤K6 < 5), moderate (5≤K6 < 13), and severe (K6≥13) mental distress. Two separate weighted multinomial logistic regression models estimated the odds of mental distress in study population (AYA vs. adult cancer survivors; and AYA vs. general population), adjusting for known covariates. Results: Mental distress was more prevalent among AYAs than adult cancer survivors (moderate: 24.0% vs 18.3%; and severe: 5.7% vs 4.2% [P= .0002]); and the general population (moderate: 24.3% vs 16.7%; and severe: 6.1% vs 5.3% [P< .0001]). Similarly, prevalence was higher among adult cancer survivors than the general population (moderate: 16.8% vs 13.6%; and severe: 3.2% vs 2.7% [P= .0002]). In the multivariable multinomial analyses, AYAs had greater odds of mental distress (aOR_moderate = 1.44; 95% CI 1.09, 1.89; and aOR_severe = 1.77; 95% CI 1.21, 2.58) vs. adult cancer survivors. AYAs also had greater odds of mental distress vs. the general population (aOR_moderate = 1.39; 95% CI 1.08, 1.79), but no significant difference in severe distress. Conclusions: About 1-in-4 AYA cancer survivors report some mental distress, and distress is more prevalent among this younger age group than older adults with cancer and the general population. Psychosocial care may be especially needed in this younger population to mitigate adverse psychosocial outcomes.