The purpose of this study is to compare the postmortem changes in computed tomography (CT) findings between normal spleen, splenic infarct, and splenic tumor infiltration. The institutional review board approved this study, and informed consent was obtained from the next of kin. We studied 63 consecutive subjects who underwent antemortem CT, postmortem CT, and autopsy between February 2012 and December 2013. Postmortem CT was performed within 1678 min after death and was followed by pathological studies. The subjects were divided into three groups based on the pathological findings: normal, splenic infarct, and splenic tumor infiltration. The volume and attenuation of the spleen were compared between antemortem and postmortem CT using paired t tests. Gender, age, time elapsed since death, and the causes of death were examined as potential confounding factors of the postmortem changes in volume and attenuation. In all groups, the spleen decreased in volume and attenuation increased on postmortem CT compared with antemortem CT. The postmortem changes in spleen volume and attenuation were not significantly associated with sex, age, time elapsed since death, or causes of death. Spleen volume decreased and attenuation increased on postmortem CT compared with antemortem CT in subjects with a normal spleen, splenic infarct, or splenic tumor infiltration. These results should caution us against underestimating the significance of splenomegaly on postmortem CT, misinterpreting reduced splenic volume as the presence of hypovolemic or distributive shock in the subject while alive, and confusing postmortem splenic hyperattenuation with diseases characterized by this finding.