Purpose: Despite its implications for quality of life, temperament, and character in multiple sclerosis are underexplored. We aimed to explore temperament and character traits, their association with clinical characteristics, and explore the factors that impact depression in patients with relapsing-remitting multiple sclerosis (RRMS).Material and Methods: This cross-sectional study enrolled 67 patients (male/female=12/55) (median age=30 (18-53)) and 50 age-and gender-matched healthy controls (HCs) (male/female=16/34) (median age= 26.5 (18-60)) using a convenience sampling method. Temperament and Character Inventory, Beck Depression and Beck Anxiety Inventories, and Structured Clinical Interview for DSM-Axis I Disorders-SCID-I were applied. Results: In the patient group there were 45 MS patients with no psychiatric comorbidity (MSN) and 22 MS patients with psychiatric comorbidity (MSP). Higher self-forgetfulness was observed in the MSP group compared with MSN and HC groups. MSP and MSN demonstrated higher total harm avoidance than HCs. MSP group showed lower total self-directedness compared with HCs. While EDSS, duration of disease, or the number of relapses did not impact depression scores; higher anxiety (Β=0.416) and lower purposefulness (Β=-1.565) significantly impacted them (R2=.50, F=32.459). Conclusion: Temperament and character differences were observed in patients with and without psychiatric comorbidity. Higher anxiety levels and the difficulty to establish and attain meaningful goals may relate to higher depression levels. Future studies with larger samples examining coping, health behaviors, and resilience as potential mediators or moderators between self-forgetfulness and psychiatric disorders may aid in defining interventions for psychiatric disorders. Adequate treatment of anxiety symptoms and addressing purposefulness are potential targets for planning behavioral interventions.