Objectives: Multiple Sclerosis (MS) is a chronic disease which affects physical,psychological and socialfunctioning of patients. In this study we aim to indicate psychiatric comorbidity, some psychosocial factorsand their associations with quality of life in patients with MS.Methods: A total of 227 patients underwent psychiatric examination and the following scales were applied:Socio-demographic data form, Hospital Anxiety and Depression Scale (HADS), Multiple Sclerosis Quality ofLife-54 (MSQOL-54), Psychosocial Adjustment to Illness Scale-Self report (PAIS-SR) and MultidimensionalScale of Perceived Social Support (MSPSS).Results: Among 227 patients with MS, 67.8% (n = 154) had psychiatric diagnosis; 24.2% (n = 55) haddepression,19.8% (n = 45) had adjustment disorder, 14.9% (n = 34) had anxiety disorder, 7.1% (n=16) haddysthymic disorder and 1.8% (n = 4) had bipolar disorder. Patients with a psychiatric diagnosis had lowerscores in role limitations due to emotional problems, emotional well-being, health perceptions, social function,cognitive function, health distress and mental health composite of MSQOL-54. PAIS-SR and MSPSS scoreswere significantly lower in MS patients with a psychiatric diagnosis. PAIS-SR scores were negatively correlatedwith role limitations-emotional, emotional well-being, social function, sexual function, satisfaction with sexualfunction, physical health composite and mental health composite scores of MSQOL-54. MSPSS total scorewas positively correlated with emotional well-being score of MSQOL-54.Conclusions: In MS patients, there is a high prevalence of psychopathology and it is associated with qualityof life, perceived social support and psychosocial adjustment of the patients. Quality of life is reduced especiallyin emotional and mental aspects in patients with a psychiatric diagnosis. Diagnosis and treatment ofpsychopathology in MS patients seems crucial to decrease disease burden.