The independent acquisition of endothermy in synapsids and diapsids are major events in vertebrate evolution since they were the driving force of a suite of correlated changes in anatomical, physiological, behavioural and ecological traits. While avian endothermy is assumed to have occurred at the archosauriform node, the acquisition of mammalian endothermy is poorly constrained both temporally and phylogenetically. Among the many unequivocal anatomical correlates of endothermy in synapsids, the presence of insulative pelage or respiratory turbinates only allows discrete inferences of presence/absence of endothermy. The analysis of bone histology allows richer palaeobiological inferences. We described the osteohistology and growth patterns of Moghreberia nmachouensis and two related taxa (Lystrosaurus and Oudenodon) for comparative purposes. Our observations suggest increasing growth rates from Moghreberia [the presence of incipient fibrolamellar bone (FLB) in humerus and femur], to Lystrosaurus (the presence of well-developed FLB in the femur but the presence of incipient FLB in the humerus), to Oudenodon (the presence of well-developed FLB in humerus and femur). However, qualitative histology does not allow reliable inferences about the occurrence of endothermy. We performed the first quantitative inferences of resting metabolic rates on fossil synapsids (M. nmachouensis as a model and Lystrosaurus and Oudenodon for comparative purposes) using quantitative histology (size, shape and density of osteocyte lacunae) combined with phylogenetic eigenvector maps. Our inferences are consistent with our qualitative histological observations: the mass-independent resting metabolic rate inferred for M. nmachouensis (2.58 mLO2 h−1 g−0.67) is lower than the value inferred for Lystrosaurus (3.80 mLO2 h−1 g−0.67), which is lower than that inferred for Oudenodon (4.58 mLO2 h−1 g−0.67). Optimization of these inferences onto a phylogenetic tree of tetrapods using the parsimony method allowed us to better constrain the temporal (more than 260 Myr ago) and phylogenetic (Neotherapsida) frames of the acquisition of mammalian endothermy.