While efforts are being currently underway for the practical identification of oxylipins esterified to complex lipids , a recent work by Watrous et al. reported the dereplication of free oxylipins by molecular networking using a high resolution mass spectrometry (HRMS) directed non-targeted approach, thanks to 234 reference tandem mass spectra of 234 of commercially available oxylipins, and a few NEO-PUFAs. Interestingly, they reported the discovery of more than 500 novel oxylipins (called "putative" in the text). This number should have raised more interest to the community, as it is believed that very little gap remains for novel oxylipin structures. We initially hypothesized that the lack of MS/MS libraries for NEO-PUFAs could partially explain the "putative" oxylipins number. Although a large amount of knowledge over the last 25 years has been accumulated concerning the relevant NEO-PUFAs detected by LC-MS/MS, it appears impossible to gather full spectra MS/MS data from either the reports of their discovery or from their synthetic preparation. Knowing that targeted MRM (multiple reaction monitoring) on low resolution mass spectrometry is preferred for quantification of NEO-PUFAs, full MS/MS data repositories could seem irrelevant at the time of their discovery. However very few of those discovered NEO-PUFAs were made available making todays dereplication not feasible. This problematic is recurrent in the field, and a recent investigation proved the importance of data repositories . Recent studies towards the development and optimization of analytical strategies based on HRMS showed great promises, and improvement of spectrometer sensitivity will surely keep on improving allowing mainstream use. As part of our continuing interest in NEO-PUFA chemistry, we developed a streamlined molecular networking dereplication pipeline based on the implementation of a MS/MS library that we named non-enzymatic oxylipins MS/MS library (NEO-MSMS). It contents an in-house collections of synthesized and unique NEO-PUFA standards, commercially available enzymatic oxylipins, and a curated MS/MS data collection of commercially available oxylipins from Watrous et al. study . Moreover, in vitro non-enzymatic oxidation of the four main PUFA (AA, eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA] and α-Linolenic acid [ALA]) lead to the creation of a vast MS/MS database of NEO-PUFAs which was sought to extend the coverage signature of oxylipins. This data descriptor presents the deposition of all this data in Zenodo and MASSIVE repositories along with its subsequent technical validation. Additionally, we also present the inclusion of the NEO-MSMS library into the GNPS libraries augmented with putatively annotated MS/MS oxylipin spectra extracted from the in vitro oxidation (Figure ). We believe this information could set the ground for understanding the importance of building a MS/MS library dedicated to oxygenated PUFA metabolites, and we hope natural product researchers, organic chemists and lipidomists in the field to share their collections, expand and use NEO-MSMS.