The adsorption of phosphatidylcholines (PCs), dissolved in squalene or squalane as organic phases, was studied at the interface with water. Using profile analysis tensiometry, the equilibrium adsorption isotherms, minimum molecular interfacial areas and solubility limits were derived. For squalene, differences in PC solubility and interfacial adsorption were found, depending on PC saturation. Compared to saturated PCs, unsaturated PCs showed a 3 fold lower interfacial density, but up to 30 fold higher critical aggregation concentration (CAC). In addition, the solubility limit of unsaturated PC in squalene and in its saturated form squalane diverged by a factor of 700. These findings provided evidence for steric repulsion or p-p (Pi-Pi) interactions of p (Pi) bonds in both solvent and solute or both effects acting complementarily. In squalane, low solubilities, but high interfacial densities were found for all investigated PCs. Changes in fatty acid chain lengths showed that the influence of the increase in entropy and enthalpy on solubility is much smaller than solvent/solute interactions. Oxidation products of squalene lowered interfacial tension, but increasing concentrations of PC expelled them from the interface. The CAC of saturated PC was increased by oxidation products of squalene while that of unsaturated PCs was not. Our findings indicate that oxidation of triglycerides in lipoprotein cores can lead to increased solubility of saturated phospholipids covering the lipoproteins, contributing to destabilization, coalescence, and terminally the formation of atherosclerotic plaques. The consideration of solvent/solute interactions in molecular modeling may contribute to the interfacial tension and the corresponding kinetic or thermodynamic stability of lipoproteins. Measured areas per molecule prove that PCs form monolayers of different interfacial densities at the squalene/water interface, but multilayers at the squalane/water interface. These findings showed that combinations of solvent or solute saturation affect the outcome for nanoemulsions forming either expanded or condensed monolayers or multilayers.