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Background: The unique psychosocial needs of parents and caregivers of young children with cancer are poorly understood. The aims of the present study were to examine health-related quality of life (HRQOL), stress, and psychological distress in parents of young children (0–4 years) diagnosed with cancer; and the associations between parent psychosocial functioning and child treatment characteristics. Methods: Parents (n = 35) with a child (n = 19 male, 54.3%) 0–48 months of age (median: 31.06 months) on active cancer therapy were recruited. Parents completed questionnaires related to demographics, parent HRQOL, parenting stress, posttraumatic stress symptoms, and parent psychological distress. Results: Parents reported clinically elevated parenting stress (5.9%), posttraumatic stress symptoms (18.2%), and psychological distress (21.9%). Compared with population norms, parents reported lower HRQOL in the vitality (t = 5.37, p < 0.001), mental health (t = 4.02, p < 0.001), role limitation–emotional (t = 3.52, p < 0.001), and general health perceptions (t = 2.25, p = 0.025) domains. Social functioning (β = 0.33, p = 0.041) predicted general health perceptions; vitality (β = 0.30, p = 0.134) and parent mental health (β = 0.24, p = 0.285) did not [F_(3,29) = 12.64, p < 0.001, R² = 0.57]. Conclusions: A subset of parents of young children on active cancer treatment experience clinically elevated psychosocial symptoms. Having poor social connections put parents at risk of perceiving their health more poorly in general. Supports that focus on preventing the emergence of clinically significant distress should focus on parents of young children with cancer who are most at risk of poor outcomes. Full article