Despite increased worldwide popularity of keeping reptiles as pets, we know little about hematologic and biochemical parameters of most reptile species, or how these measures may be influenced by intrinsic and extrinsic factors. Blood samples from 43 wild-caught pythons (Morelia spilota imbricata) were collected at various stages of a 3-yr ecological study in Western Australia. Reference intervals are reported for 35 individuals sampled at the commencement of the study. As pythons were radiotracked for varying lengths of time (radiotransmitters were surgically implanted), repeated sampling was undertaken from some individuals. However, because of our ad hoc sampling design we cannot be definitive about temporal factors that were most important or that exclusively influenced blood parameters. There was no significant effect of sex or the presence of a hemogregarine parasite on blood parameters. Erythrocyte measures were highest for pythons captured in the jarrah forest and at the stage of radiotransmitter implantation, which was also linked with shorter time in captivity. Basophil count, the only leukocyte influenced by the factors tested, was highest when the python was anesthetized, as was globulin concentration. Albumin and the albumin:globulin ratio were more concentrated in summer (as was phosphorous) and at the initial stage of radiotransmitter placement (as was calcium). No intrinsic or extrinsic factors influenced creatinine kinase, aspartate aminotransferase, uric acid, or total protein. This study demonstrates that factors including season, location, surgical radiotransmitter placement, and anesthetic state can influence blood parameters of M. s. imbricata. For accurate diagnosis, veterinarians should be aware that the current reference intervals used to identify the health status of individuals for this species are outdated and the interpretation and an understanding of the influence of intrinsic and extrinsic factors are limited.