Background: The prevalence and functional burden of the chronic demyelinating disease multiple sclerosis (MS) are well documented; however, little is known about the initial clinical course of alertness, sleep, cognitive, and psychological symptoms.Objectives: This exploratory, prospective, longitudinal study multidimensionally investigated the development and progression of alertness, sleep, fitness to drive, and psychological symptoms in the first year after de novo MS diagnosis.Methods: Twenty-five people with MS (pwMS) were assessed cognitively, psychologically, and using polysomnography soon after diagnosis and one year later, with outcomes compared to matched healthy controls. Results: In the early stage of the disease, psychological symptoms of pwMS were comparable with those of controls, and patient conditions did not deteriorate within the first disease year. A small percentage of pwMS experienced increased levels of anxiety and depression after diagnosis. Alertness, sustained attention, and fitness to drive were comparable between both groups, and fatigue levels remained low over the course of the year.Conclusions: This study highlights patient experiences within the initial clinical course of MS in a small group of patients. Further research is needed to understand the progression of symptoms and impairments in MS over a longer period and in different stages of the disease.