BACKGROUND: Both depression and sexual dysfunction (SD) may be present in patients with multiple sclerosis (MS). ----- OBJECTIVE: The aim of this study was to evaluate a possible association between SD and depression in patients with MS in Croatia. ----- SUBJECTS AND METHODS: This was a prospective cross-sectional study carried out in tertiary healthcare centre over 10 months, which included 101 consecutive pwMS (mean age 42.09 (range 19-77) years, 75 female, 26 male, EDSS score 3.1 (range 0.0-7.0)). SD was assessed using Multiple Sclerosis Intimacy and Sexuality Questionnaire (MSISQ), which was for this purpose successfully translated and validated into Croatian. Information on treatment for depression was obtained during the medical interview. Data were analysed and interpreted using parametric statistics (IBM Corp. Released 2015. IBM SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp.). ----- RESULTS: 89 patients completed MSISQ. 25 patients were in treatment for depression, while 75 did not have depressive symptoms. On MSISQ 57 (43women, 14 men) patients had responded with ‘almost always/ always’ suggestive of SD. Majority of patients reported primary SD, followed by secondary and tertiary SD. Most difficulties were found regarding difficulty in getting or keeping a satisfactory erection (34.6% (N=9) men), followed by 32.9% (N=27) reporting that it takes too long to orgasm or climax, followed with bladder or urinary symptoms in 32.6% (N=29). There were no significant differences between female and male patients regarding treatment for depression (􀀀2=0.018, df=1, p>0.05). Results in all subcategories on t-test found that depressive patients had higher impact on SD when compared to non-depressive: overall (t=-2.691, df=87, p<0.01) and in regards to primary (t=-2,086, df=87, p<0.05), secondary (t=-2.608, df=87, p<0.05) and tertiary (t=-2.460, df=86, p<0.05) SD. Depressive patients on 7 questions showed significantly (p<0.05) higher SD symptoms: Muscle tightness or spasms in my arms, legs, or body; Tremors or shaking in hands or body; Pain, burning, or discomfort in their body; Feeling less attractive; Fear of being rejected sexually because of MS; Lack of sexual interest or desire; Less intense or pleasurable orgasms or climaxes. ----- CONCLUSIONS: This study gives insight into the presence of depression and SD in Croatian patients with MS for which purpose valid questionnaire for the assessment of SD in MS patients MSISQ was with permission successfully translated and validated into Croatian. The connection between depression and SD must be considered when managing patients with MS.