Over the last few decades, there has been a dramatic increase in hematological malignancies (HMs) in the population of Sardinia. It is accepted that oxidative stress biomarkers have been demonstrated to be prognostically important in various neoplastic diseases. The aim of this study is to evaluate serum vitamin E, total antioxidant capacity (TAC), Malondialdehyde (MDA) and reactive oxygen species (ROS) levels in 80 Sardinian patients with different HMs [acute myeloid leukemia (AML)(n=20), myelodysplastic syndromes (MDS) (n=20), Hodgkin lymphoma (HL) (n=20) and non-Hodgkin lymphoma (NHL) (n=20)] on the day of their diagnosis. Samples from all participants were obtained after an overnight fast (at least 10 hours). This study was approved and conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. Patients and controls provided written, informed consent before entering the study. All study participants' medical history and their medication were documented upon enrolling. Lower levels of TAC and Vitamin E were observed in most of the studied groups compared to healthy controls (0.41-0.49 mmol/L vs. 0.56 mmol/L) (19.55-28.55 μmol/L vs. 34.51 μmol/L). Moreover, higher average MDA levels were observed in HL and NHL patients compared to healthy controls (16.6 ng/ml-17.8 ng/ml vs. 7.4 ng/ml). Additionally, the ROS values of all studied groups were found elevated. Serum TAC showed significant negative correlations with MDA values (R= -0.51; P<0.001). Statistical significance was observed in all hematological parameters, producing either positive or negative correlation with at least one OS biomarker. The present data suggest that Sardinian patients with HL and NHL on the day of their diagnosis presented the highest OS in comparison to AML and healthy subjects. Moreover, MDS patients presented high OS status. Likewise, our results also indicated that changes in their hematological indices are eminent of their oxidative and antioxidative status.