The purpose of this paper is to identify immunologic hallmarks of excessive bodyweight. The analysis is based on 176 adults (106 women, 70 men) who participated in a nested case-control study in Italy. All participants were healthy at the time of blood collection and aged between 36 and 75 years. We employed multivariate analysis of variance and a nonparametric Bayesian additive regression tree approach along with a receiver operating characteristic (ROC) curve analysis to determine the immunologic signature of excessive body weight (i.e., obesity and overweight). Interleukin 8 (IL-8), IL-10, interferon γ, and inducible protein 10 were shown to be predictive of excessive body weight with an area under the ROC curve of 71% (p < 0.0002). We propose that by using this profile-based approach to define immunologic signatures, it might be possible to identify unique immunologic hallmarks of specific types of obesity.