Oxygen-16 (¹⁶O) is a stable isotope of oxygen, having 8 neutrons and 8 protons in its nucleus. It has a mass of 15.99491461956 u. Oxygen-16 is the most abundant isotope of oxygen and accounts for 99.762% of oxygen's natural abundance.^[2] The relative and absolute abundance of ¹⁶O are high because it is a principal product of stellar evolution and because it is a primordial isotope, meaning it can be made by stars that were initially made exclusively of hydrogen. 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 to make ¹⁶O. The neon-burning process creates additional ¹⁶O. Oxygen-16 is doubly magic.

Solid samples (organic and inorganic) for ¹⁶O studies are usually stored in silver cups and measured with pyrolysis and mass spectrometry.^[3] Researchers need to avoid improper or prolonged storage of the samples for accurate measurements.^[3]

Oxygen-16 was originally the standard from which the atomic masses of all nuclides were defined, i.e., one atomic mass unit was defined as 1⁄16 the mass of oxygen-16, though the atomic mass unit has since been redefined relative to carbon-12.