: Studies have shown that the clinical impact of JAK2 inhibitors in primary myelofibrosis patients is due to the regulation of cytokine levels, suggesting that cytokine profiles might play a critical role in myeloproliferative neoplasms physiopathology. In this study, we compared the plasma cytokine profiles of Polycythemia Vera (PV) patients and Essential Thrombocythemia (ET) patients as a function of their JAK2 V617F status and the presence of thrombohemorrhagic complications. Using a multiplex cytokine assay, cytokine measurements were taken of the plasma of seventeen PV patients and twenty-one ET patients. Twenty-two of these patients (10 PV and 12 ET) experienced at least one thrombohemorrhagic manifestation before diagnosis. We showed that cytokine levels were significantly increased in PV and ET patients compared to normal values and that several positive correlations existed between the cytokine concentrations and the biological parameters in each MPN. The comparison between the cytokine profiles of ET and PV patients showed a statistical significant increase of IL-4, IL-8, GM-CSF, IFN-γ, MCP-1, PDGF-BB and VEGF in the ET group. Only TFN-α and PDGF-BB were specifically impacted by the JAK2 V617F status of the PV and ET patients, respectively, suggesting that there are both JAK2 V617F-driven and JAK2 V617F-independent inflammatory responses in MPN. We also showed that the subgroup of PV patients with vascular complications displayed significantly different concentrations of IL-12(p70) and GM-CSF compared to patients without vascular complications. Altogether, these data suggest that cytokine measurement might be useful for the clinical and therapeutic stratification of PV and ET patients.