When in contact with biological fluids, nanoparticles dynamically absorb biomolecules like proteins and lipids onto their surface, forming a "corona". This biocorona is a dynamic and complex structure that determines how host cells respond to nanoparticles. Despite the common use of mouse models in pre-clinical and toxicological experiments, the impact of corona formed in mouse serum on the biophysical and biological properties of different size NP has not been thoroughly explored. Furthering the knowledge on the corona formed on NP exposed to mouse serum proteins can help in understanding what role it might have in in vivo studies at systemic, tissue, and cellular levels. To investigate biocorona formation, different sized polystyrene NP were exposed to mouse serum. Our data show a size- and time-dependent protein and lipid corona formation. Several proteins were identified and apolipoproteins were by far the most common group on the NPs surfaces. Moreover, we observed that cholesterol and triglycerides effectively bind to NP emphasizing that proteins are not the only biomolecules with high-affinity binding to nanomaterial surfaces. These results highlight that further knowledge on NP interactions with mouse serum is necessary regarding the common use of this model to predict the in vivo efficiency of NP.