Malaria has been an important disease throughout the history, particularly in the Mediterranean. The island of Sardinia (Italy) was characterized by severe endemic malaria from antiquity until its eradication in 1950. It provides an exceptional and unique site to examine the history of the disease and its effects on human biology and ecology. Endemic malaria can cause chronic hemolytic anemias that may result in osteological signatures. This paper examines these markers, Porotic Hyperostosis (PH) and Cribra Orbitalia (CO), which are identified from skeletons uncovered in archaeological excavations in Northern Sardinia. Previous hypotheses based on historical references and genetic data suggest that the disease was absent on the island in prehistory and was imported, probably by slaves, during the Carthaginian period (6th to 3rd century BC). This article reports on the paleontological analysis of 283 skeletons excavated from seven archeological sites dating from 4700 BP to 1582 AD. Osteological remains were examined for markers CO and PH as a proxy variable for malaria. The findings support previous hypotheses about history of malaria over time.