Background: Relinquishing control (RC) of outcomes to God is a long-standing form of religious coping with serious illness. Placing cancer outcomes in God's hands has been positively related to coping and quality of life (QOL). However, the mechanisms involved in this relationship have not been established. A serial mediation model [i.e., RC (X)-Meaning/Peace (M1)-Coping Efficacy (M2)-Symptoms, Physical QOL, Functional QOL (Ys)] tested the hypothesis that Meaning/Peace alone and in conjunction with coping would mediate the RC-QOL relationship.Method: 548 persons with a cancer diagnosis completed the Religious Problem-Solving Scale (RPSS), FACIT-Sp Meaning and Peace Scales, Cancer Behavior Inventory (coping efficacy), and measures of Physical Quality of Life (PQOL), Functional Quality of Life (FQOL) and Symptoms.Results: As hypothesized, the single mediation effects of Meaning/Peace were significant [Indirect Effects: PQOL: .23 (95% CI: 0.15, 0.34); FQOL: 0.46 (95% CI: 0.33, 0.61); Symptoms:-0.18 (95% CI:-0.27, -0.10)]. In addition, mediation was confirmed for the serial mediation model (i.e., Meaning/Peace -Coping Efficacy as serial mediators) with significant indirect effects [Indirect Effects: PQOL: 0.37 (95% CI: 0.27, 0.48); FQOL: 0.57 (95% CI: 0.42, 0.72); Symptoms:-0.25 (95% CI:-0.35, -0.17)].Conclusions: In the mediation models tested, the RC-QOL and RC-Symptoms relationships were mediated by the confluence of a sense of peace perhaps due to patients' feelings that outcomes were in God's hands and a sense of coherence between their current situation and a spiritually-based meaning system. Meaning/Peace was also related to coping efficacy, suggesting that these mediating constructs could be used to inform evidence-based interventions, such as Meaning-Centered therapies, that are sensitive to the belief systems of cancer patients and enhance QOL.