Abstract Accurate measurements of the molecular composition of single cells will be necessary for understanding the relationship between gene expression and function in diverse cell types. One of the most important phenotypes that differs between cells is their size, which was recently shown to be an important determinant of proteome composition in populations of similarly sized cells. We therefore sought to test if the effects of cell size on protein concentrations were also evident in single cell proteomics data. Using the relative concentrations of a set of reference proteins to estimate a cell’s DNA-to-cell volume ratio, we found that differences in cell size explain a significant amount of cell-to-cell variance in two published single cell proteome datasets.