Aims: Stress is one of the significant factors contributing to the onset, exacerbation, and recurrence of Multiple Sclerosis (MS) that imposes high costs on society and people. The present study aims to assess the role of spiritual intelligence, sense of coherence, and cognitive flexibility (internal resources) in predicting perceived stress in patients with MS. Methods & Materials: In this descriptive/correlational study, 156 patients with MS were selected as samples using a convenience sampling method. The participants completed the Perceived Stress Scale (PSS), Spiritual Intelligence Self-Report Inventory (SISRI), Sense of Coherence Scale (SOC), and Cognitive Flexibility Inventory (CFI). The collected data were analyzed using descriptive and inferential statistics (stepwise regression analysis) in SPSS v. 24. Findings: Transcendental awareness (a component of SISRI), meaningfulness (a component of SOC), and perception of controls and alternatives (components of CFI) predicted perceived stress in MS patients. Conclusion: In stress management program, internal resources education can help reduce perceived stress in patients with MS.