BackgroundIt is essential to investigate cognitive deficits in multiple sclerosis (MS) to develop evidence-based cognitive rehabilitation strategies. Here we refined cognitive decline assessment using the automated tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) and hierarchical cluster analysis.MethodsWe searched for groups of distinct cognitive profiles in 35 relapsing-remitting MS outpatients and 32 healthy controls. All individuals participated in an automated assessment (CANTAB) and in a pencil and paper general neuropsychological evaluation.ResultsHierarchical cluster analysis of the CANTAB results revealed two distinct groups of patients based mainly on the Simple Reaction Time (RTI) and on the Mean Latency of Rapid Visual Processing (RVP). The general neuropsychological assessment did not show any statistically significant differences between the cluster groups. Compared to the healthy control group, all MS outpatients had lower scores for RTI, RVP, paired associate learning, and delayed matching to sample. We also analyzed the associations between CANTAB results and age, education, sex, pharmacological treatment, physical activity, employment status, and the Expanded Disability Status Scale (EDSS). Although limited by the small number of observations, our findings suggest a weak correlation between performance on the CANTAB and age, education, and EDSS scores.ConclusionsWe suggest that the use of selected large-scale automated visuospatial tests from the CANTAB in combination with multivariate statistical analyses may reveal subtle and earlier changes in information processing speed and cognition. This may expand our ability to define the limits between normal and impaired cognition in patients with Multiple Sclerosis.Electronic supplementary materialThe online version of this article (10.1186/s12883-018-1141-1) contains supplementary material, which is available to authorized users.