There are three known stable isotopes of oxygen (8O): 16O, 17O, and 18O.
 Radioactive isotopes ranging from 11O to 28O have also been characterized, all short-lived. The longest-lived radioisotope is 15O with a half-life of 122.266(43) s, while the shortest-lived isotope is the unbound 11O with a half-life of 198(12) yoctoseconds, though half-lives have not been measured for the unbound heavy isotopes 27O and 28O.
 Natural oxygen is made of three stable isotopes, 16O, 17O, and 18O, with 16O being the most abundant (99.762% natural abundance). Depending on the terrestrial source, the standard atomic weight varies within the range of [15.99903, 15.99977] (the conventional value is 15.999).
 16O has high relative and absolute abundance because it is a principal product of stellar evolution and because it is a primary isotope, meaning it can be made by stars that were initially hydrogen only. Most 16O is synthesized at the end of the helium fusion process in stars; the triple-alpha process creates 12C, which captures an additional 4He nucleus to produce 16O. The neon burning process creates additional 16O.
 Both 17O and 18O are secondary isotopes, meaning their synthesis requires seed nuclei. 17O is primarily made by burning hydrogen into helium in the CNO cycle, making it a common isotope in the hydrogen burning zones of stars. Most 18O is produced when 14N (made abundant from CNO burning) captures a 4He nucleus, becoming 18F. This quickly (half-life around 110 minutes) beta decays to 18O making that isotope common in the helium-rich zones of stars. About 109 kelvin is needed to fuse oxygen into sulfur.
 An atomic mass of 16 was assigned to oxygen prior to the definition of the unified atomic mass unit based on 12C. Since physicists referred to 16O only, while chemists meant the natural mix of isotopes, this led to slightly different mass scales.
 Measurements of 18O/16O ratio are often used to interpret changes in paleoclimate. Oxygen in Earth's air is 99.759% 16O, 0.037% 17O and 0.204% 18O. Water molecules with a lighter isotope are slightly more likely to evaporate and less likely to fall as precipitation, so Earth's freshwater and polar ice have slightly less (0.1981%) 18O than air (0.204%) or seawater (0.1995%). This disparity allows analysis of temperature patterns via historic ice cores.
 Solid samples (organic and inorganic) for oxygen isotopic ratios are usually stored in silver cups and measured with pyrolysis and mass spectrometry. Researchers need to avoid improper or prolonged storage of the samples for accurate measurements.
 Due to natural oxygen being mostly 16O, samples enriched with the other stable isotopes can be used for isotope labeling. For example, it was proven, that the oxygen released in photosynthesis originates in H2O, rather than in the also consumed CO2, by isotope tracing experiments. The oxygen contained in CO2 in turn is used to make up the sugars formed by photosynthesis.
 In heavy water reactors the neutron moderator should preferably be low in 17O and 18O due to their higher neutron absorption cross section compared to 16O. While this effect can also be observed in light water reactors, ordinary hydrogen (protium) has a higher absorption cross section than any stable isotope of oxygen and its number density is twice as high in water as that of oxygen so that the effect is negligible. As some methods of isotope separation enrich not only heavier isotopes of hydrogen but also heavier isotopes of oxygen when producing heavy water, the concentration of 17O and 18O can be measurably higher. Furthermore the 17O(n,α)14C reaction is a further undesirable result of an elevated concentration of heavier isotopes of oxygen. Therefore facilities which remove tritium from heavy water used in nuclear reactors often also remove or at least reduce the amount of heavier isotopes of oxygen.
 Oxygen isotopes are also used to trace ocean composition and temperature which seafood is from.
 Thirteen radioisotopes have been characterized; the most stable are 15O with half-life 122.266(43) s and 14O with half-life 70.621(11) s. All remaining radioisotopes have half-lives less than 27 s and most have half-lives less than 0.1 s. Four heaviest known isotopes (up to 28O) decay by neutron emission to
24O, whose half-life is 77.4(4.5) ms. This isotope, along with 28Ne, have been used in the model of reactions in crust of neutron stars. The most common decay mode for isotopes lighter than the stable isotopes is β+ decay to nitrogen, and the most common mode after is β− decay to fluorine.
 Oxygen-13 is an unstable isotope, with 8 protons and 5 neutrons. It has spin 3/2−, and half-life 8.58(5) ms. Its atomic mass is 13.024815(10) Da. It decays to nitrogen-13 by electron capture, with a decay energy of 17.770(10) MeV. Its parent nuclide is fluorine-14.
 Oxygen-14 is the second most stable radioisotope. Oxygen-14 ion beams are of interest to researchers of proton-rich nuclei; for example, one early experiment at the Facility for Rare Isotope Beams in East Lansing, Michigan, used a 14O beam to study the beta decay transition of this isotope to 14N.
 Oxygen-15 is a radioisotope, often used in positron emission tomography (PET). It can be used in, among other things, water for PET myocardial perfusion imaging and for brain imaging. It has an atomic mass of 15.0030656(5), and a half-life of 122.266(43) s. It is produced through deuteron bombardment of nitrogen-14 using a cyclotron.
 Oxygen-15 and nitrogen-13 are produced in air when gamma rays (for example from lightning) knock neutrons out of 16O and 14N:
 15O decays to 15N, emitting a positron. The positron quickly annihilates with an electron, producing two gamma rays of about 511 keV. After a lightning bolt, this gamma radiation dies down with half-life of 2 minutes, but these low-energy gamma rays go on average only about 90 metres through the air. Together with rays produced from positrons from nitrogen-13 they may only be detected for a minute or so as the "cloud" of 15O and 13N floats by, carried by the wind.
 Oxygen-20 has a half-life of 13.51±0.05 s and decays by β− decay to 20F. It is one of the known cluster decay ejected particles, being emitted in the decay of 228Th with a branching ratio of about (1.13±0.22)×10−13.