Apatemyids are known from the Paleocene and Eocene of Europe, and the Paleocene to Oligocene of North America, and may share a special relationship with Euarchontoglires. The only endocast previously described for an apatemyid pertains to Carcinella sigei from the late Eocene of France. Here we present a composite virtual endocast of Labidolemur kayi derived from high-resolution X-ray computed tomography data, based on partial crania from the late Paleocene (Clarkforkian) and early Eocene (Wasatchian) of the Clarks Fork Basin, Wyoming. Like C. sigei, L. kayi had voluminous, transversely expansive olfactory bulbs, accounting for approximately 12–15% of the endocranial volume. This is similar to Cretaceous eutherians, but contrasts with the relatively smaller olfactory bulbs in both the basal gliran Rhombomylus turpanensis and in primitive primates (Ignacius graybullianus, Microsyops annectens). Similar to R. turpanensis, I. graybullianus, and the inferred ancestral condition for Microsyops, but unlike C. sigei, L. kayi exhibited exposed caudal colliculi, supporting the inference that this condition was primitive for Euarchontoglires and Euarchonta. The cranial capacity of L. kayi is estimated at 0.5–0.6 cc, yielding encephalization quotient (EQ) estimates of 0.23–0.28 or 0.42–0.50 depending on the equation used. These values are much lower than estimates for C. sigei, suggesting significant increase occurred in brain size in Apatemyidae, perhaps related to elaborations in the family's specialized manual extractive feeding regime. Similarities with primitive primates in EQ and the inferred position of the rhinal sulcus may allow for inferences about encephalization and neocorticalization in the common ancestor of Euarchontoglires.