Background: Multiple sclerosis (MS) is a chronic demyelinating central nervous system (CNS) disease. Changes in insulin growth factor 1 (IGF-1) input to the brain can affect survival of myelin and CNS cells. The study aims to investigate the relation of serum IGF-1 levels with cognitive impairment and fatigue in MS patients. Methods: This study was conducted on 46 MS patients and 46 healthy controls. All participants were subjected to clinical assessment, serum IGF-1 levels, expanded disability status scale (EDSS), modified fatigue impact scale (MFIS), and Montreal cognitive assessment (MoCA) scale. Results: There was no significant difference between patients and controls regarding serum IGF-1 levels (P = 0.19). However, low serum levels of IGF-1 have significantly greater odds for fatigue (P = 0.002) and cognitive impairment (P < 0.001). Also, serum IGF-1 levels have a significant negative correlation with MFIS (r = − 0.701 and P < 0.001) and a significant positive correlation with MoCA scale (r = + 0.84 and P < 0.001). Conclusions: The results, specifically that low levels of serum IGF-1 was associated with cognitive impairment and fatigue in MS, suggest that IGF-I may be involved in the pathogenesis of cognitive deficits and fatigue in MS disease.