The glass transition of sucrose in 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE)/sucrose mixtures was studied by differential scanning calorimetry. Mole ratios of 1:2, 1:1, and 2:1 DOPE/sucrose mixtures were dehydrated at osmotic pressures ranging from 41 to 311 MPa through vapor-phase equilibration. Two glass transitions were observed in 1:2 DOPE/sucrose mixtures that were dehydrated at osmotic pressures > 81 MPa. The first glass transition temperature (T-g) was lower than that of pure sucrose solutions that were dehydrated under identical conditions. The second T-g of the 1:2 DOPE/sucrose mixture was similar to the T-g of sucrose solutions that were dehydrated in the absence of DOPE. In the 2:1 and 1:1 DOPE/sucrose mixtures, only one T-g was observed at a temperature lower than that of pure sucrose. We propose that depression of the T-g of sucrose in the DOPE/sucrose mixtures is the result of a confinement effect that occurs in the sucrose solution that is sequestered in the aqueous cores of the hexagonal II phase of DOPE with a radius of similar to2 nm.