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Background/Objective Cognitive fatigability (CF) affects many with Multiple Sclerosis (MS), yet measurement remains challenging due to poor correlation with subjective fatigue reports. MSReactor cognitive screening platform offers potential for objective CF assessment, particularly for longitudinal monitoring in clinical settings.Objective To determine whether changes in error rates during sustained cognitive testing provide a platform for studies investigating CF and its relationship to disease progression.Methods Adults with relapsing-remitting and secondary-progressive MS were recruited from seven Australian tertiary MS clinics. Participants completed MSReactor cognitive testing battery: a simple reaction time, a choice reaction time, and a One back test (OBK, which is a measure of working memory). Each test required participants to make 32–35 responses to stimuli appearing on screen. CF was quantified as a sustained doubling of incorrect responses in the last third compared to first third of OBK test. Expanded Disability Status Scale (EDSS) was assessed as part of standard care.Results Among 836 participants, 113 (13.5%) demonstrated a sustained doubling of errors in OBK task over follow-up period (median 890 days, IQR: 1070). Of these, 7 participants with sustained increases in intra-test error rates subsequently had a 6-month confirmed disability progression event.Conclusion This study explores MSReactor as an objective measure of CF in MS. We identified a group of participants who consistently made more errors in latter third of a sustained working memory test, which appeared independent of future disability progression. Further research is needed to validate this finding against clinical correlates and work productivity.