Background: Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by demyelination and axonal damage within the central nervous system. Relapsing-remitting MS (RRMS) comprises 70–80% of cases, marked by episodic neurological deficits separated in time and space. Acute stressors have been implicated in precipitating MS relapses, yet the interplay between life stress and relapse risk remains incompletely understood. Objectives: To compare life stress index between RRMS patients during relapse and remission and to assess the predictive value of stress for relapse occurrence. Methods: In this cross-sectional comparative study, 60 RRMS patients (30 in relapse, 30 in remission) were assessed for Demographics, clinical history, neurological deficits, Expanded Disability Status Scale (EDSS), and life stress index. Results: 60 patients were divided equally into relapse and remission groups. Females and rural residents were significantly more prevalent in the relapse group (P = 0.004 and 0.018, respectively). The relapse group had a significantly elevated median EDSS score (4 vs. 1; P < 0.001). Psychiatric symptoms such as depression and anxiety were more frequent in the relapse group but not statistically significant. The life stress index was significantly elevated in the relapse group (median: 218 vs. 130; P < 0.001) and positively correlated with EDSS. Logistic regression identified life stress index as an independent predictor of relapse (OR: 1.8; P < 0.001). Conclusions: In our study, Life Stress index was significantly elevated in relapsing-remitting MS patients during relapses than remission. And it predicted relapse risk.