Human exposure to electromagnetic fields (EMFs) has risen considerably during the last decades, because of the industrial and technical development and the consequent increase of artificial EMFs sources. In particular, blood is largely involved in the environmental EMF exposure, because it is located everywhere in the human body. Lympho-monocyte cells are blood components that protect the human organism against infections. In this study, we investigate biochemical changes in lympho-monocyte cells extracted from human peripheral blood after exposure to EMFs at 1.8 GHz frequency and 200 V/m electric field strength for times ranging from 5 to 20 h inside a reverberation chamber. Some mixtures of cells, coming from many human subjects, were exposed and successively investigated by means of Raman micro-spectroscopy technique and principal components analysis. The spectral analysis was able to detect variations of the biochemical composition of the nucleus of exposed cells. Such modifications are mainly detectable as an intensity decrease of some DNA and nucleic acid Raman peaks with respect to the intensity of some protein peaks and they were most evident in the case of 20 h exposed samples. These results were in agreement with the increase of reactive oxygen species (ROS) production, observed in the exposed cells. Overall, the obtained results point out that EMFs exposure may induce modifications of the DNA in some blood cells of long-term exposed people.