The interactions of the nonsteroidal anti-inflammatory drug, celecoxib, with 1,2-distearoyl-sn-glycero-3-phosphocholine multilamellar vesicles were studied as a function of temperature and different drug concentrations, using Fourier transform infrared spectroscopy, differential scanning calorimetry, and turbidity technique at 440 nm. Our studies reveal that celecoxib lowers the main phase-transition temperature and decreases the fluidity of the membranes at all concentrations. Celecoxib induced opposing effects on molecular order at different concentrations by increasing the ordering of the system at low concentrations and disordering it at high concentrations. Further, the drug increases the number of hydrogen bonds around the carbonyl groups at low concentrations in both phases, whereas the degree of dehydration increases at high concentrations in the gel phase. An evidence of phase separation has also been clearly observed at high concentrations. Thus, depending on the concentration used, celecoxib induces significant changes in the biophysical properties of membranes that may aid in understanding its mechanism of action.