This study investigated the specific association of stressful life events (SLE) and experiential avoidance (EA) with depression in patients with mental disorders. It also analyzed the possible mediating role of depression in the relation of EA to well-being and life satisfaction. A total of 147 patients (mean age = 40.16 years) diagnosed with anxiety, mood or adjustment disorder were recruited from a mental health centre. They completed measures of SLE, EA, depression, well-being and life satisfaction. Regression analyses showed that SLE and EA were positively related to depression (R
2 = .45), although the contribution made by EA was higher (β = .61, p < .001) than the one made by SLE (β = .19, p < .01). Bootstrap mediation analyses revealed that there was an indirect effect from EA to physical well-being (B = –4.52, SE = .70, p < .001, 95% CI [–6.03, –3.20]) and satisfaction (B = –.14, SE = .02, p < .001, 95%, CI [–.19 –.09]) through depression. This indirect effect was less consistently supported with respect to emotional well-being (B = –3.33, SE = .48, p < .001, 95%, CI [–4.30, –2.41]). These findings give support to the hypothesis that EA could be an important factor contributing to depression in patients with mental disorders. The results also provide evidence that depression seems to play an important mediational role when considering the negative impact that EA exerts on patients´ well-being and satisfaction.