The Mediterranean Sea is one of the most studied regions in the world in terms of microplastic (MP) contamination. However, only a few studies have analysed the chemical composition of MPs at the Mediterranean Sea surface. In this context, this study aims to describe the chemical composition as a function of particle size, mass and number concentrations of MPs collected in the surface waters of the Mediterranean Sea. The chemical composition showed a certain homogeneity at the Mediterranean Sea scale. The main polymers identified by Fourier Transform Infra-Red (FTIR) spectroscopy were poly(ethylene) (67.3 ± 2.4%), poly(propylene) (20.8 ± 2.1%) and poly(styrene) (3.0 ± 0.9%). Nevertheless, discrepancies, confirmed by the literature, were observed at a mesoscale level. Thus, in the North Tyrrhenian Sea, the proportion of poly(ethylene) was significantly lower than the average value of the Mediterranean Sea (57.9 ± 10.5%). Anthropic sources, rivers, or polymer ageing are assumed to be responsible for the variations observed.