In organic photovoltaic (OPV) devices, the open-circuit voltage (V-oc) is one of the most important parameters that determines the device performance. Generally, the maximum value of V-oc is set by the energy gap (E-gap). However, the E-gap value of the active layer of an operating device will deviate from that based on the energy levels of the individual materials due to the occurrence of complicated interfacial physical and chemical interactions. Here, we systematically investigated the effects of the interfacial energy band alignment with different polymer donors and small-molecule acceptors. The E-gap values increased in the presence of an interfacial dipole, leading to a larger voltage loss (Delta) than expected.