Oxylipins such as isoprostanes (IsoPs), prostaglandins (PGs) and thromboxanes (TXs) are lipid mediators derived from the oxidation of polyunsaturated fatty acids, which regulate the magnitude of oxidative stress and inflammation processes and play an important role in pathophysiological processes in the kidney. A total of 36 oxylipins were analyzed by UHPLC-QqQ-MS/MS in the urine of 41 renal recipients from cadaveric donors of the Nephrology Unit of the University Hospital Virgen de la Arrixaca during the first six months after renal transplantation, in order to investigate several candidate oxylipins as more accurate and predictive biomarkers in renal transplantation than classical biological variables. A decrease in nine PGs, mostly from the AA-D pathway (p < 0.05) and one IsoP: 15-keto-15-F2t-IsoP (p < 0.001) was observed. Moreover, two PGs (2,3-dinor-11β-PGF2α and 17-trans-PGF3α) increased between five days and six months after renal transplantation (p < 0.05). In addition, when kidney function improved, a positive correlation between oxylipin levels and the excretion of urine proteins was observed. These results suggest that oxylipins could be useful markers for monitoring renal function in the post-renal transplantation period. These findings could be of utility not only for the development of strategies for long-term preservation of graft function, but also for innovative and alternative therapies -using oxylipins as predictive markers-to avoid organ rejection.