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The aim of the present study is to describe how religiosity and spirituality affect the psychiatric morbidity of Muslim intensive care unit (ICU) patients. We conducted a prospective nationwide cross-sectional study of ICU patients discharged from 45 medical centers spanning 31 proivinces in Iran. Adults (age ≥ 18 years) admitted to the ICU and treated with invasive mechanical ventilation were eligible. Nine validated survey tools were administered to detect direct and indirect associations between spiritual health (SH) and depression, anxiety, and post-traumatic disorder. The Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale-Revised (IES-R), Post-Traumatic Stress Syndrome 14 question (PTSS-14) quality-of-life (QoL), and quality of patient to physician or nurse communication (PP-QoC and PN-QoC) scales were modeled through two mediators by structural equation modeling (SEM). Sex, ICU type, LOS, and APACHE II score were added in the independent variable list. 338 eligible patients were discharged from the ICUs during the study period. 56 were excluded (clinical status), and 282 were administered the survey. 278 returned it, with 272 complete and 6 partial responses. SH displayed no direct or indirect association to QoL. SH was indirectly associated with decreased depression and anxiety (B = - 0.081, p < 0.05) via PP-QoC mediator. Both direct and indirect positive associations were observed between SH and IES-R (B = 0.293, p < 0.05; via PP-QoC) and PTSS-14 scores (B = 0.267, p < 0.001; via PP-QoC). Medical ICU location was associated with decreased PTSS-14 scores via the same mediator. In this survey of Muslim ICU patients treated with invasive mechanical ventilation, SH correlated with decreased depression and anxiety, but paradoxically increased post-traumatic stress. The most influential mediator was patient-physician quality-of-communication.