Multiple sclerosis (MS) relapse diagnosis is impeded by 'pseudo-relapses' whilst relapse treatment lacks specificity. Before we can improve clinical care, we must first improve our understanding of relapse pathogenesis. Currently, the circulatory immune mechanisms underpinning relapse are poorly understood. We aimed to determine changes in circulatory cell counts from people with MS during relapse versus remission and their association with clinical outcomes. Data was collected retrospectively by screening 2316 patient files through which we identified 78 episodes of MS relapse and remission. From these participants full blood examination data, we calculated immune cell counts and ratios. In participants with contrast enhancing lesions on magnetic resonance imaging (MRI, n = 38), total neutrophil count (p = 0.04) and neutrophils/total white cell count (N%) was higher (p = 0.04) in relapse versus remission. Similarly, in participants with a new lesion on MRI (n = 51), total neutrophil count (p = 0.01) was significantly higher during relapse versus remission. Univariable regression analyses demonstrated that lymphocytes, the neutrophil to lymphocyte ratio, monocytes/total white cell count (M%) and N% were all associated with changes in disability scores whilst multivariable regression analyses demonstrated that M% was associated with the presence of contrast enhancing lesions. This study determined that neutrophils are elevated in the circulation of people with MS during relapse compared to remission. Additionally, neutrophils, monocytes and lymphocytes were found to be associated with clinical outcomes of relapse. These findings support the notion that alterations in circulating immune cells may play a role in MS relapse pathogenesis and may inform future biomarker studies.