In this study Raman spectroscopy has been used to monitor the changes in erythrocytes and plasma during Plasmodium infection in mice, following malaria disease progression over the course of 7 days. The Raman spectra of both samples are dominated by the spectra of hemoglobin and hemozoin, due to their resonant enhancement. In plasma samples, due to the inherently low heme background, heme-based changes in the Raman spectra could be detected in the very early stages of infection, as little as one day after Plasmodium infection, where parasitemia levels were low, on the order of 0.2%, and typically difficult to detect by existing methods. Further principal component analysis also indicates concurrent erythrocyte membrane changes at around day 4, where parasitemia levels reached 3%. These results show that plasma analysis has significant potential for early, quantitative and automated detection of malaria, and to quantify heme levels in serum which modulate malarial effects on the immune system.