Mechanisms underlying variability in patient’s responses to platelet transfusions are not fully understood. To characterize platelet transfusion induced changes on plasma proteins, we used plasma proteomics to study the effect of 1) autologous platelet transfusions in healthy volunteers in absence and presence of controlled endotoxemia, and of 2) allogenic platelet transfusions in haemato-oncologic patients. Longitudinal plasma profiling revealed intra-individual variation in healthy volunteers, but no impact of autologous transfusions. Controlled endotoxemia induced by lipopolysaccharide (LPS) exposure in healthy volunteers elicited a shared acute phase response across all recipients, which was characterized by increased abundance of two distinct protein clusters. However, this did not result in transfusion-specific responses on plasma protein levels. Likewise, plasma proteomic profiling of paired samples from haemato-oncological patients prior- and post-administration of allogenic transfusions revealed intra-individual variation and a transfusion-specific response that remained limited to platelet basic protein (PPBP). We found a positive association of haptoglobin levels (HP, ρ = 0.61) and a negative association of extracellular superoxide dismutase [Cu-Zn] levels (SOD3, ρ = -0.62) prior transfusion to corrected count increments (CCI) at 1h and 24h, respectively. Taken together, platelet transfusions did not induce specific changes in plasma protein levels in controlled endotoxemia but were associated with increased levels of platelet-associated proteins in haemato-oncological patients. Importantly, no additional changes in plasma protein profiles, which could be associated with inflammation or dysregulated processes, were observed following platelet transfusions.