Postcranial morphology of Paleogene lipotyphlans (Mammalia: Laurasiatheria) is poorly known relative to dental morphology. When these elements can be referred, they have proven to be a rich source of data for phylogenetic and ecological inferences. In particular, tarsal morphology has challenged hypothesized relationships of several taxa. We refer isolated tarsals from several early and late Uintan (middle Eocene) localities in the San Diego area to three genera of sespedectine erinaceomorph lipotyphlan, Crypholestes, Proterixoides, and Sespedectes, based on patterns of size, morphology, and abundance. Astragali and calcanei are confidently referred to all three genera, whereas naviculars are more tentatively referred to Proterixoides and Sespedectes, and cuboids to Sespedectes. Tarsals of the three genera are morphologically nearly uniform, supporting their hypothesized close relationship. The most significant difference is a relatively longer calcaneal tuber in Proterixoides. The tarsal morphology of Sespedectinae is most consistent with an unspecialized terrestrial locomotor repertoire. Some distinctive features of the sespedectine tarsus, such as ‘S’-shaped ectal facets and a prominent tuber tibialis on the navicular, are potentially indicative of lipotyphlan affinities. However, there is no support for an exclusive relationship to extant erinaceids (or any other lipotyphlan family) or to other Paleogene erinaceomorphs (Macrocranion, Zionodon). Phylogenetic analysis confirms that sespedectines are most likely relatively basal lipotyphlans and that Erinaceomorpha is not a natural group. SUPPLEMENTAL DATA—Supplemental materials are available for this article for free at www.tandfonline.com/UJVP Citation for this article: Penkrot, T. A., and S. P. Zack. 2016. Tarsals of Sespedectinae (?Lipotyphla) from the middle Eocene of southern California, and the affinities of Eocene ‘erinaceomorphs’. Journal of Vertebrate Paleontology. DOI: 10.1080/02724634.2016.1212059.