Coxibs are a group of non-steroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase 2 inhibitors, characterized by a much lower gastrotoxicity compared to classic NSAIDs. They are often used in conjunction with other drugs, which greatly increases the likelihood of adverse drug interactions. The presented study analyzed the degradation rate of celecoxib and cimicoxib in solutions under the influence of other medicinal substances at different temperatures. For this purpose, triple-drug mixtures were prepared, consisting of coxib and eleven different commonly used drugs (paracetamol, ketoprofen, diclofenac, acetylsalicylic acid, ibuprofen, meloxicam, tramadol, doxycycline, bisoprolol, and caffeine). Then, the mixtures were incubated at two temperatures. Within the time specified by the research plan, further aliquots of the mixtures were subjected to a chromatographic analysis. Separation was conducted on HPTLC F254 silica gel chromatographic plates as a stationary phase, using chloroform: acetone: toluene as a mobile phase, and was detected densitometrically at wavelengths of 254 nm. The percentage changes in the tested coxibs content, depending on the time and conditions of incubation, were presented. Based on the obtained data, the basic kinetic parameters of the degradation processes were determined. The celecoxib and cimicoxib showed a relatively high durability in changing environmental conditions. It was observed that the rate of decomposition of cimicoxib and celecoxib in the tested mixtures was different and depended on the temperature and presence of other components, with cimicoxib turning out to be a more stable compound.