Background: Previous research has suggested that children who are exposed to chronic stress are at greater risk for childhood obesity, however little research has examined the mechanism of this association. This study aimed to investigate the association between family and household stress during the COVID-19 pandemic and children’s BMIz, and whether children’s hair cortisol concentration (HCC) mediates this association.

Methods: This study used baseline data from 228 children 2–6 years from the Family Stress Study, a prospective cohort study of families with children 2–6 years. Parents responded to an online survey which assessed family and household stressors including family functioning, home chaos, financial insecurity, food insecurity, parental depression, parenting stress, stressful life events, and COVID-19 stressors. A total family chronic stress index score was calculated from parents’ responses on these measures. Hair samples were collected from children to assess their HCC. The Hayes PROCESS mediation macro was used to assess the total, direct, and indirect effect of the family chronic stress index on child BMIz, adjusting for household income and child ethnicity/race.

Results: We found that the family chronic stress index was associated with higher child BMIz (b = 0.815, 95% CI = 0.181–1.449), but this association was not mediated by children’s HCC (b = 0.004, CI = −0.042–0.076).

Conclusions: Future research should continue to investigate hair cortisol as a measure of chronic stress among children younger than 6 years and explore other mechanisms of how chronic stress is associated with children’s weight outcomes, such as through parenting practices that influence children’s eating behaviour or physical activity, or children’s weight-related behaviours.