Objective: To assess the neuropsychological status of pediatric multiple sclerosis (MS) patients and its relationship with clinical variables in a longitudinal study. Methods: Patients with MS (n = 46) and age- and gender-matched healthy control subjects (HCs, n = 53) were given tests of non-verbal reasoning, attention/concentration, visuospatial judgement and verbal fluency at baseline visit and after 2 years of follow-up. Cognitive impairment was defined as a failure on at least three of the four tests. Patients were grouped according to the age of disease onset (<= 12 years as group 1 and > 12 years as group 2). Results: Cognitive impairment was detected in 22 of 46 patients at follow-up (47.8%). Patients with cognitive worsening had higher EDSS scores at follow-up compared to cognitively improved/stable group (0.68 +/- 1.16 vs 0.04 +/- 0.2, p = 0.01). The most affected domains were attention/concentration and non-verbal reasoning. Comparison between baseline and follow-up tests showed impairment in non-verbal reasoning over time in group 1 patients while other functions improved over time in patient and control groups as expected. Conclusion: Pediatric MS is likely to affect patients' cognition concurrently with their disability levels. This effect is significant in the non-verbal reasoning area in patients with disease onset before age 12 years. A practical method assessing this function should be part of these patients' regular follow-up for optimal treatment, prevention and rehabilitation.