Elite performing exercise requires an intricate modulation of the blood pressure to support the working muscles with oxygen. We have previously identified a genomic regulatory module that associates with differences in blood pressures of importance for elite performance in racehorses. This study aimed to determine the effect of the regulatory module on the protein repertoire. We sampled plasma from 12 Coldblooded trotters divided into two endothelial regulatory module haplotype groups, a sub-elite performing haplotype (SPH) and an elite performing haplotype (EPH). By sampling each at rest and exercise, we aimed to quantify the regulatory module's effect on blood pressure. The haplotype groups and their interaction were interrogated in two analyses, i) individual paired ratio analysis for identifying differentially abundant proteins of exercise (DAPE) and interaction (DAPI) between haplotype and exercise, and ii) unpaired ratio analysis for identifying differentially abundant protein of haplotype (DAPH). At an expression fold change >1.5, our analyses identified 39 (DAPE), 53 (DAPH) and 20 (DAPI) proteins that showed significantly different expression levels (p-value ≤ 0.05). The proteomics analyses revealed a widespread change in plasma protein content during exercise, regardless of haplotype status, with a decrease tendency in protein abundance that mainly related to lung function, tissue fluids, metabolism, calcium ion pathway and cellular energy metabolism. Furthermore, we provide the first investigation of the proteome variation due to interaction between exercise and related blood pressure haplotypes, which this difference was related to a faster switch to the lipoprotein and lipid metabolism during exercise for EPH. The molecular signatures identified in the present study contribute to improved understanding of the biological mechanisms behind exercise and exercise-related blood pressure regulation of the module that affect racing performance in horses.