Objective: To examine the impact of perceived limitations, stigma and sense of coherence on quality of life in multiple sclerosis patients. Design: Cross-sectional survey. Setting: Department of Neurology, University Medical Center Groningen, the Netherlands. Subjects: Multiple sclerosis patients. Main measures: World Health Organization Quality of Life - abbreviated version, Stigma Scale for Chronic Illness, Sense of Coherence Scale, background and disease-related questions. Results: In total, 185 patients (61% response rate) participated in the study with moderate to severe limitations. Stigma was highly prevalent but low in severity. Patients with a higher sense of coherence experienced a lower level of limitations (B = -0.063, P < 0.01) and less stigma (enacted stigma B = -0.030, P < 0.01; self-stigma B = -0.037, P < 0.01). Patients with a higher level of limitations experienced more stigma (enacted stigma B = 0.044, P < 0.05; self-stigma B = 0.063, P < 0.01). Patients with a higher sense of coherence experienced better quality of life (physical health B = 0.059, P < 0.01; psychological health B = 0.062, P < 0.01; social relationships B = 0.052, P < 0.01; environmental aspects B = 0.030, P < 0.01). Patients with a higher level of limitations experienced poorer quality of life (physical health B= -0.364, P < 0.01; psychological health B = -0.089, P< 0.05) and patients with more stigma also experienced poorer quality of life (self-stigma: physical health B = -0.073, P < 0.01; psychological health B = -0.089, P < 0.01; social relationships B = -0.124, P < 0.01; environmental aspects B = -0.052, P < 0.01, and enacted stigma: physical health B = -0.085, P < 0.10). Conclusion: Patients with less perceived limitations and stigma and a higher level of sense of coherence experienced better quality of life. Patients with a higher sense of coherence experienced a lower level of limitations and less stigma.