Disaccharides play an important role in survival of anhydrobiotic organisms during extreme environmental conditions. A key protection feature is their capability to form the hydrogen bond (HB) network in a similar fashion as the one made by water. Since various ions also affect the HB network in completely hydrated systems, it is of a great interest to understand how they impact preservation when incorporated in a disaccharide network. To address this, we employ a combination of experimental and modeling techniques to study behavior of multilamellar 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) liposomes freeze-dried with sucrose in presence of NaCl or NaH2PO4·H2O at various concentrations (0.01–1 M). Differential scanning calorimetry (DSC) was employed in order to determine the cooperative unit size (CUS), the number of lipid molecules that constitute a domain of cooperative motion in the liposome, and the melting temperature (Tm). In the absence of salt CUS was estimated to be 122 ± 12, whereas in the presence of NaCl CUS increases more (347 ± 34 for c = 1 M) than for NaH2PO4·H2O (193 ± 26 for 1 M). When it comes to Tm, the situation is reversed; NaCl induces increase by about 1 K, while NaH2PO4·H2O by about 10 K. These findings clearly demonstrate how different interaction forces−hydrogen bonding, charge pairing, and van der Waals interactions between acyl chains−affect CUS and Tm. Their interplay and contribution of particular interaction was further analyzed with molecular dynamics (MD) simulations. This analysis demonstrated that the HB network of DMPC and sucrose is partially disrupted in the presence of NaCl ions, and even to a greater extent in the case of NaH2PO4·H2O ions. Notably, H2PO4− ions outcompete and replace the sucrose molecules at the DMPC surface, which in turn alters the nature of the DMPC-surrounding interactions, from a weaker HB-dominated to a stronger CP-dominated interaction network.