This study aimed to carry out a comparative evaluation of the hematological profile (erythrocyte count, hemoglobin concentration, hematocrit, and Wintrobe index parameters such as mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration), in addition to certain biochemical parameters (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, scrum total protein, albumin, glucose, total cholesterol, and triglycerides), in the Italian mullet Mugil cephalus (Linnaeus 1758) and the Turkish mullet Chelon auratus (Risso 1810). Accordingly, two groups of fish were used in this study: 30 flathead grey mullets, M. cephalus, caught in Lake Faro, Italy, and 30 golden grey mullets, C. auratus, caught in the estuarine channel system of Keycegiz-Dalyan, Turkey. Statistical evaluations (unpaired t-test) revealed that there were no significant differences in weight or total length values between the two mullet groups. However, the differences between all the evaluated blood parameters (except alanine aminotransferase) between the Italian and the Turkish mullet were significant (P < 0.0001). The present study demonstrated that there were significant hematological and biochemical differences between the Italian (M. cephalus) and the Turkish (C. auratus) mullet. Our findings also contribute to expanding the knowledge on the hematology and biochemistry of two different species of mullet originating from two different habitats. Since the evaluation of blood parameters represents an essential tool in examining the effects of environmental conditions on fish physiology and, consequently, on fish health status, further research in this field is encouraged and would be very useful.