Interactions between the binary combinations of sodium dodecyl sulfate (SDS) or dimethyldodecylammoniopropane sulfonate (DPS) with -α-phosphatidylcholine (PC), 1,2-didecanoyl-sn-glycero-3-phosphacholine (DPC), and 1,2-dipalmitoyl-sn-glycero-3-phosphacholine (PPC) at the air/water interface and in aqueous bulk were evaluated with the help of interfacial tension (γ) and pyrene fluorescence (I₁/I₃) measurements by studying the aggregation processes of SDS and DPS in pure water and in the presence of 7–36 μM of each lipid. The γ measurements suggested that the interface was mainly occupied by the surfactant monomers especially in the presence of PC and PPC, and the surfactant–PC or surfactant–PPC aggregates were mainly available in the bulk with the least surface activity. Significant surface activity was observed in the case of a surfactant–DPC complex. The fluorescence measurements showed clear onset, C₁, and completion, C₂, of a vesicles solubilization process upon incorporation of surfactant monomers into the vesicles in the presence of DPC and PPC whereas this process was not visible in the presence of PC. A comparative study of all the three lipids indicated that both PC and PPC were mainly available in the aggregated form in the bulk due to their higher hydrophobicities and, hence, were the least surface active. On the other hand, DPC with relatively lower hydrophobicity showed considerable surface activity even in the monomeric form. Among both surfactants, DPS showed stronger interactions with DPC and PPC in comparison to SDS due to its zwitterionic nature, which could easily accommodate itself into the lipid-aggregated assemblies with similar headgroup natures, and helped in reducing the interheadgroup repulsions.