The retina is a notable tissue with high metabolic needs which relies on specialized vascular networks to protect the neural retina while maintaining constant supplies of oxygen, nutrients and dietary essential fatty acids. Here we determined the lipid content of the developing mouse retina under healthy and pathological angiogenesis using the oxygen-induced retinopathy model (OIR). In the OIR model, pathological angiogenesis is induced in mice through their exposure to variable oxygen levels. Thus, mouse pups with their nursing mothers were kept at 75% O2 from postnatal day 7 (P7) until day 12 (P12). Mice were then returned to ambient air (20.8% O2) and retinas (N=6) were collected at different time points (P12, P12.5, P15 and P17) and used in a lipid extraction procedure. Retinas from mouse pups under physiological development (controls) were also collected. Total lipid extracts were then used for a comprehensive non-targeted lipidomic analysis, whose quantitative results for 300 lipid species are presented here (‘Inague and Alecrim et al - Lipidomics Data’ spreadsheet). Lipidomics data was integrated with previously obtained transcriptomics data (SRA: SRP155931; BioProject: PRJNA483866). By matching the lipid profile to changes in the mRNA transcriptome, we identified a lipid signature associated with oxygen-induced retinopathy. Our data show that pathological angiogenesis leads to intense lipid remodeling favoring pathways for neutral lipid synthesis, cholesterol import/export and lipid droplet formation. The lipid signature also indicates that, from its early stages, pathological angiogenesis induces profound changes in pathways for the production of long-chain fatty acids, vital for retinal homeostasis. The net result is the production of large quantities of mead acid, a marker of essential fatty acid deficiency, which might also be an important marker for retinopathy severity. In sum, our lipid signature might contribute to a better understanding of many diseases of the retina that lead to vision impairment or blindness. This lipid signature might also be important for the development of additional translational therapies for retinopathy and other angiogenesis-dependent diseases.