Elevated child and caregiver psychopathology are observed in families of children with cancer, with a subset developing clinically significant symptoms. This study examines whether caregivers' resting respiratory sinus arrhythmia (RSA) and observed emotion regulation (ER) are protective against caregiver and child psychopathology during the first year of pediatric cancer treatment. Primary caregivers of children recently diagnosed with cancer (N = 159; child Mage = 5.6 years; children 48% male, 52% female) completed 12 monthly questionnaires. At Month 3, primary caregivers were interviewed about their experiences of emotions, and their resting RSA was measured. Data were analyzed using multilevel models. Observed ER was associated with lower caregiver anxiety, depression, and posttraumatic stress symptoms (PTSS) 1 year postdiagnosis but was not associated with children's symptoms. Resting RSA had a significant positive association with child depression/anxiety at the start of treatment and Month 12 child PTSS. Findings suggest that caregivers would benefit from interventions to manage their negative emotions at the start of cancer treatment. Additionally, caregivers who are more physiologically regulated may be more attuned to their children's negative emotions. Our findings highlight the importance of taking a multimethod approach to understanding how ER impacts functioning. (PsycInfo Database Record (c) 2023 APA, all rights reserved).