In ruminants, the survival and development of the conceptus are heavily dependent on the composition of the uterine lumen fluid (ULF), which is influenced by prostaglandins (PGs). However, the variations in underlying PG-mediated ULF remain unclear. Herein, cycling heifers received an intrauterine infusion of vehicle as a control (CON) or meloxicam (MEL) on days 12-14 of the estrous cycle. Then, the ULF was collected on day 15 and alternations in its protein and lipid levels were analyzed. The suppression of prostaglandins induced by meloxicam resulted in 1343 differentially abundant proteins (DAPs) and 59 differentially altered lipids. These DAPs were primarily associated with vesicle-mediated transport, immune response, and actin filament organization, and were mainly concentrated on the ribosome, complement and coagulation cascades, cholesterol metabolism, chemokine signal pathway, regulation of actin cytoskeleton and starch and sucrose metabolism. These differential lipids reflected a physiological metabolic shift as the abundance of cell membrane-related lipids was modulated, including an accumulation of triacylglycerols and reductions in lysophosphatidylcholines, hexosyl ceramides, ceramides, and sphingomyelins species. Integration analysis of the DAPs and differentially altered lipid metabolites revealed that glycerophospholipid metabolism and choline metabolism were the core pathways. These findings highlight the potential roles of prostaglandins in ULF, providing new insights into the contributions of prostaglandins in the development of the conceptus.