Holistic human proteome maps are expected to complement comprehensive profile assessment of health and disease phenotypes. However, methodologies to analyze proteomes in human tissue or body fluid samples at relevant scale and performance are still limited in clinical research. Their deployment and demonstration in large enough human populations are even sparser. In the present study, we have characterized and compared the plasma proteomes of two large independent cohorts of obese and overweight individuals using shotgun MS-based proteomics. One cohort comes from a Canadian single-center clinical weight management program while the other one belongs to a multicenter pan-European weight loss study (i.e., the DiOGenes study for which MS proteomic data have been already deposited to the ProteomeXchange Consortium with the dataset identifier PXD005216). The MS proteomic data deposited herein corresponds to the cohort coming from the Weight Management Clinical program of The Ottawa Hospital.