Injecting low salinity brines is regarded as an enhanced oil recovery (EOR) process through IFT reduction. However, the exact mechanism behind this process is an unsettled and complex issue that has not been well understood yet, especially for heavy crude oil system. Besides, limited information is available regarding the key heavy oil/brine interfacial tension (IFT). The present study aims to investigate the sensitivity of dead heavy crude oil/brine IFT to a wide range of properties/conditions and to reveal the underlying physicochemical mechanisms involved in enhanced oil recovery and IFT reduction by low salinity water injection into heavy oil reservoir. IFT was measured as a function of salinity, temperature, and pressure by means of the IFT 700 apparatus making available the use of the state-of-the-art axisymmetric drop shape analysis (ADSA) technique for the pendant drop case. Meanwhile, the individual effects of monovalent and divalent ions were also investigated.The results indicate a conflict between salt and surface-active agents resulting in critical salt concentration where the IFT value is the minimum, beyond which brine dilution has a negative impact on IFT. In addition, our study illustrates that in all concentrations of salt, higher IFT values are obtained using CaCl2 compared to NaCl aqueous solution, which is more intensive and apparent at higher concentrations. Furthermore, there is a strong inverse relationship between temperature and IFT, but a slightly increasing behavior with respect to pressure. The range of brine concentration in which the heavy oil/brine IFT is minimized is vital for successful design of low salinity water injection.