The surface pressure (pi)-area (A) and surface potential (Delta V)-A isotherms were measured for two-component monolayers made of dipalmitoylphosphatidylcholine (DPPC)/single-chain (perfluorooctyl)pentanol (F8C50H) and DPPC/single-chain (perfluorooctyl)pentylphosphocholine (F8C5PC) on a substrate solution of 0.15 M NaCl at 293.2 K as a function of the composition of the two components. The Langmuir method and the ionizing electrode method were used. The data for these systems were analyzed using an additivity rule. Assuming a regular surface mixture, the Joos equation, which allows description of the collapse pressure of a monolayer made of two miscible components, was used to establish the miscibility within the monolayer. An interaction parameter and an interaction energy were calculated. The two-component DPPC/F8C5OH and DPPC/F8C5PC monolayers were miscible. Furthermore, the mean molecular area, surface potential, and phase diagrams enabled us to determine the molecular orientation of DPPC/F8C5OH and DPPC/F8C5PC in the monolayer. Two types of phase diagrams were obtained and classified into the positive azeotropic and negative azeotropic types. Fluorescence microscopy (FM) and Brewster angle microscopy (BAM) for the DPPC/F8C5OH and DPPC/F8C5PC systems show that both systems can dissolve the ordered micrometer-size solid DPPC domains. However, morphological analyses using atomic force microscopy (AFM) suggest partial miscibility or phase separation for DPPC and the partially fluorinated compounds on the nanometer scale. In particular, triskelion-shaped domains were evidenced for F8C50H. These results indicate that the partially fluorinated amphiphiles investigated here fluidize the DPPC monolayer upon lateral compression and that these chemicals may be useful to develop their innovative applications in the biomedical field.