Interactions in binary mixed monolayers from lipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and amphiphilic poly(2-methyloxazoline)-block-poly(dimethylsiloxane)-block-poly(2-methyloxazoline) block copolymers were studied by using the Langmuir balance technique and Brewster angle microscopy. It is shown that monolayers from the saturated lipid (DPPC) are more sensitive to the presence of polymers in the film, resulting in phase separation and the formation of pure lipid domains at high surface pressure. The morphology and composition of such phase-separated lipid-polymer films were studied by fluorescence microscopy and ToF-SIMS. In contrast, in DOPC-containing monolayers, the polymers tend to phase-separate at low surface pressures only and homogeneous films are obtained upon further compression, due to higher lipid fluidity. The analysis of excess energy of mixing shows that while the separation effect in densely packed DPPC-containing films is strongly dependent on the polymer size (with the larger polymer having a much stronger influence), in the case of monolayers with DOPC much smaller effects are observed. The results are discussed in terms of the monolayer composition, lipid fluidity, and polymer size.