Vedolizumab, a gut-selective integrin antagonist, is an effective therapy for inflammatory bowel disease (IBD), but immune correlates of treatment response remain poorly understood. We performed longitudinal immune profiling of blood and serum from 20 vedolizumab-treated IBD patients (15 Crohn’s disease, 5 ulcerative colitis) to characterize treatment-associated immune changes and identify baseline features associated with clinical response. Samples were collected at baseline and week 14. Immune cell phenotyping was performed using five 10-color flow cytometry panels, while serum proteomics was assessed with the Olink^® 96 Inflammation panel. Age- and sex-matched healthy controls (HCs) were included for comparison. IBD patients could be distinguished from HCs based primarily on immune cell profiles, whereas serum proteomic differences were less pronounced. Vedolizumab treatment induced modest changes in immune cell composition and serum proteins. Clinical responders exhibited shifts in three immune populations and a reduction in CXCL8 and IL-6 levels by week 14. Unsupervised hierarchical clustering of five baseline immune cell populations stratified patients into two groups that broadly corresponded with treatment outcome. Furthermore, non-responders exhibited increased IFNγ and CXCL9 levels. However, these immune cell populations and proteins did not remain significant upon correcting for multiple testing. Taken together, we identified exploratory immune and cytokine patterns associated with vedolizumab response that may support the development of precision medicine approaches in IBD.