The Church of the Second Hytoth is a religious organization that practices the Ortothan religion. The central beliefs of the religion are that the current universe (the "Second Hytoth") was preceded by a different universe (the "First Hytoth"), which was consumed by an extrauniversal entity. A group of survivors fled to the Second Hytoth when it was created, seven of them choosing to ascend to godhood to ensure the universe's safety. These seven gods (the "Holy Seven"/"Koru-teusa" in the Ortothan language) were active in the early universe, though all have died except for one (the "Holy Fourth"/"Rakmou-leusan"). Rakmou-leusan is said to currently guard the universe from extrauniversal entities ("Voruteut") that are trying to invade.

The stated goals of the Church are to aid Rakmou-leusan, sacrificing blood to preserve their life, kill any Voruteut that successfully enter, and spread Ortothan beliefs. The organization is relatively small and pacifistic, intentionally avoiding conflict due to their size, though they are active on a global scale. The group mainly speaks the Ortothan Extraterrestrial Language (OEL), which has remained unusually unchanged compared to other languages (claimed to be the result of divine influence). Several occultists founded the Church in 1899 after encountering an extraterrestrial entity, though the religion has existed for far longer, followed by prehistoric humans and alien civilizations. Other Ortothan groups have been active in the past, none of which reached the current size of the Church.

Although the Church of the Second Hytoth is primarily active on Earth, the Ortothan religion exists on interstellar and apparently intergalactic scales. It is suspected that no single extraterrestrial group embodies the religion; there are instead countless sects with varying motives in limited contact with each other. The largest discovered sect is the Terzan 2 Ortothan Coalition, a collection of alien entities that reside in Globular Cluster Terzan 2, a cluster of stars in orbit around the Milky Way Galaxy. Current information suggests that the Coalition is composed of a large number of civilizations and independent entities that formed a loose alliance, possibly militaristic in nature, which are at war with a group known as "Twelve Stars." Until the Foundation can directly communicate with the Coalition's leaders (if they exist), all knowledge of the group is superficial.

The only extraterrestrial Ortothan group known to have entered the solar system is Species of Interest 002, which left their native star system and attempted to colonize Earth ~700 million years ago. Recovered artifacts and structures indicate that the species was highly advanced, extensively using thaumaturgy and psionics to operate their technology. Further research is limited, as few of their artifacts have survived to the present. SoI-002 is presumed to be extinct. Why the colonization failed is unknown.