The efficiency and effectiveness in any distribution network is largely determined by the performance of depots in such a network. The purpose of this study is to develop a methodological framework to evaluate the performance of distribution centers of express companies. The framework is based on Data Envelopment Analysis and was validated on a set of 44 depots of a large express service provider situated in the United Kingdom. The analysis revealed that 31 depots out of 44 are efficient. Furthermore, statistical analyses identified four factors influencing the efficiency scores of express transportation depots.