The SARS-CoV-2 pandemic has already killed more than one million people worldwide. To gain entry, the virus uses its Spike protein to bind to host hACE-2 receptors on the host cell surface and mediate fusion between viral and cell membranes. As initial steps leading to virus entry involve significant changes in protein conformation as well as in the electrostatic environment in the vicinity of the Spike/hACE-2 complex, we explored the sensitivity of the interaction to changes in ionic strength through computational simulations and surface plasmon resonance. We identified two regions in the receptor-binding domain (RBD), E1 and E2, which interact differently with hACE-2. At high salt concentration, E2-mediated interactions are weakened but are compensated by strengthening E1-mediated hydrophobic interactions. These results provide a detailed molecular understanding of Spike RBD/hACE-2 complex formation and stability under a wide range of ionic strengths.