In light of the adverse mental health impacts of the COVID-19 pandemic for parents of preschool-aged children, it is important to identify modifiable protective factors that can inform interventions for parents who continue to struggle. The present study examined prospective and concurrent associations of parental psychological flexibility (acceptance, defusion, and committed action) with measures of parental stress and depression symptoms in an international sample of parents of preschoolers assessed at three time points over the first two years of the COVID-19 pandemic: The start of the pandemic (T1) as well as the end of the first (T2) and second (T3) year of the pandemic. Consistent with hypotheses, the three measures of parent psychological flexibility (assessed at T2) prospectively predicted parenting stress levels one year later (T3) ( p < .05). Defusion and Committed Action also prospectively predicted lower levels of depression symptoms one year later [ p < .05]. Comparable concurrent analyses of data of parents who provided data at T1 and T2 (N = 79) are also presented with acceptance and defusion negatively associated with parental stress (p < .001) and defusion negatively associated with depression (p < .05). This study contributes longitudinal evidence for the value of psychological flexibility for parents and suggests that Acceptance and Commitment Therapy interventions may help to support parental mental health during sustained periods of stress such as the COVID-19 pandemic.