A photooxygenation is a light-induced oxidation reaction in which molecular oxygen is incorporated into the product(s). Initial research interest in photooxygenation reactions arose from Oscar Raab's observations in 1900 that the combination of light, oxygen and photosensitizers is highly toxic to cells. Early studies of photooxygenation focused on oxidative damage to DNA and amino acids, but recent research has led to the application of photooxygenation in organic synthesis and photodynamic therapy.

Photooxygenation reactions are initiated by a photosensitizer, which is a molecule that enters an excited state when exposed to light of a specific wavelength (e.g. dyes and pigments). The excited sensitizer then reacts with either a substrate or ground state molecular oxygen, starting a cascade of energy transfers that ultimately result in an oxygenated molecule. Consequently, photooxygenation reactions are categorized by the type and order of these intermediates (as type I, type II, or type III reactions).

Photooxygenation reactions are easily confused with a number of processes baring similar names (i.e. photosensitized oxidation). Clear distinctions can be made based on three attributes: oxidation, the involvement of light, and the incorporation of molecular oxygen into the products:

Sensitizers (denoted "Sens") are compounds, such as fluorescein dyes, methylene blue, and polycyclic aromatic hydrocarbons, which are able to absorb electromagnetic radiation (usually in the visible range of the spectrum) and eventually transfer that energy to molecular oxygen or the substrate of photooxygenation process. Many sensitizers, both naturally occurring and synthetic, rely on extensive aromatic systems to absorb light in the visible spectrum. When sensitizers are excited by light, they reach a singlet state, ¹Sens*. This singlet is then converted into a triplet state (which is more stable), ³Sens*, via intersystem crossing. The ³Sens* is what reacts with either the substrate or ³O₂ in the three types of photooxygenation reactions.

In classical Lewis structures, molecular oxygen, O₂, is depicted as having a double bond between the two oxygen atoms. However, the molecular orbitals of O₂ are actually more complex than Lewis structures seem to suggest. The highest occupied molecular orbital (HOMO) of O₂ is a pair of degenerate antibonding π orbitals, π_2px* and π_2py*, which are both singly occupied by spin unpaired electrons. These electrons are the cause of O₂ being a triplet diradical in the ground state (indicated as ³O₂).

While many stable molecules’ HOMOs consist of bonding molecular orbitals and therefore require a moderate energy jump from bonding to antibonding to reach their first excited state, the antibonding nature of molecular oxygen’s HOMO allows for a lower energy gap between its ground state and first excited state. This makes excitation of O₂ a less energetically restrictive process. In the first excited state of O₂, a 22 kcal/mol energy increase from the ground state, both electrons in the antibonding orbitals occupy a degenerate π* orbital, and oxygen is now in a singlet state (indicated as ¹O₂). ¹O₂ is very reactive with a lifetime between 10-100 μs.

The three types of photooxygenation reactions are distinguished by the mechanisms that they proceed through, as they are capable of yielding different or similar products depending on environmental conditions. Type I and II reactions proceed through neutral intermediates, while type III reactions proceed through charged species. The absence or presence of ¹O₂ is what distinguishes type I and type II reactions, respectively.

In type I reactions, the photoactivated ³Sens* interacts with the substrate to yield a radical substrate, usually through the homolytic bond breaking of a hydrogen bond on the substrate. This substrate radical then interacts with ³O₂ (ground state) to yield a substrate-O₂ radical. Such a radical is generally quenched by abstracting a hydrogen from another substrate molecule or from the solvent. This process allows for chain propagation of the reaction.