Skin is the primary interface with the external environment. To evaluate the impact of external factors like sun exposure on the cutaneous ecosystem which is composed of skin, sebum, microbiota, it must be studied as a whole to understand how they interact with each other. We developed a reconstructed human epidermal model colonized with human microbiota and sebum to reproduce the complexity of the skin ecosystem. This in vitro model was exposed to simulated solar radiation. A new SPF50+ photoprotective system containing a specific combination of four sun filters (TriAsorB, Tinosorb S, Uvinul T150 and Uvinul A+) and affording a broad spectrum UVB+A photoprotection, was evaluated on this in vitro model. Metabolomic profiles were performed by means of NMR and UHPLC-HRMS. Metagenomic analyses were performed from genomic DNA extract samples. ITS1 of the ribosomal RNA gene, and of the V1-V3 region of 16S gene were sequenced by high-speed sequencing. Metabolomic analyses revealed high skin oxidative stress with modification of glutathione and purine pathway but also urea cycle. Other pathways have been highlighted linked to skin microbiota, like BCAAs cycle, lipid metabolism and tryptophan pathway. With the new photoprotective system, metabolome of the skin was preserved and the physiological interactions within the skin ecosystem were protected from sun exposure deleterious effects. This study identified a highly accurate metabolomic signature of sun exposed skin using an in vitro model representative of the complete skin ecosystem. Metabolomic signature was correlated to metagenomic analysis of skin microbiota and explain interactions between skin and microbiota.