Experiential avoidance, cognitive defusion, and mindfulness have all been associated with psychological disorders and well-being. This study investigates whether they predict psychological distress, i.e., symptoms of burnout, depression, stress and anxiety, in parents of children with chronic conditions. We hypothesized that these factors would exhibit a large degree of common variance, and that when compared to mindfulness and defusion, experiential avoidance on its own would predict a larger proportion of unique variance. 75 parents of children with chronic conditions having burnout symptoms who participated in an intervention study completed measures of burnout, stress, anxiety, depression, experiential avoidance, cognitive defusion, and mindfulness at the beginning of the intervention study (baseline). We ran several regression analyses to assess the predictive ability of these different constructs. Experiential avoidance on its own accounted for 28–48% of the variance in different psychological symptoms. Cognitive defusion and mindfulness did not make a significant contribution to explaining burnout, stress and anxiety, but cognitive defusion contributed to explaining depression. The results confirmed our hypothesis, supporting research on the importance of psychological flexibility as a central factor in understanding the occurrence of psychological distress.