Sepermeru (or Spermeru) was a town of ancient Egypt situated roughly midway between the city of Heracleopolis to the north and Oxyrhynchus to the south in what was considered the XIX Upper Egyptian nome.

During the Ramesside Period of Pharaohs, Sepermeru enjoyed some prominence as both a largely populated religious, military, and administrative center for the XIX Nome, located near the Bahr Yusuf canal that connected the Nile with the Fayyum region (cf. S. Katary, Land Tenure in the Ramesside Period, p. 215; O'Connor, Man, Settlement and Urbanism, pp. 690–91). The meaning of the town's name ("near to the desert") signifies its status as a frontier community (cf. H. te Velde, Seth: God of Confusion, p. 118, n.2) and was thus a suitable cult center for the god Seth.

According to Wilbour Papyrus (cf. Gardiner, Commentary, 28, pp. 127–128), by Dynasty XIX there existed two land-owning temple institutions within the main Seth-enclosure at Sepermeru. The larger of these two institutions was the "House of Seth, Lord of Sepermeru," and the smaller a temple dedicated to his consort, Nephthys, and called the "House of Nephthys of Ramesses-Meriamun." It is not known how long the temple of Seth had been established in Sepermeru before Dynasty XIX, but it is evident that the temple of Nephthys was a specific foundation (or refurbishment) of Ramesses II, which dates this particular institution to that Pharaoh's reign (1279-1213 BCE).

Both temples (and their respective land-holdings) were apparently under separate administration; the Prophet Huy administered the House of Seth in Dynasty XIX and XX. Yet, as Katary notes, "What cannot be established from the evidence of P. Wilbour is the authority of any particular prophet of the House of Seth over the House of Nephthys," and: "Although Huy may have been the chief administrator of the House of Nephthys as well as his own temple, he was most certainly not in charge of the administration of the...fields of the House of Nephthys, such fields being the responsibility of two prophets of Nephthys, Merybarse...and Penpmer." (Katary, Land Tenure in the Ramesside Period, pp. 219–220).

There were at least two more subsidiary shrines in Sepermeru in Dynasties XIX and XX: a sanctuary called the "House of Seth, Powerful-is-His-Mighty-Arm," and a cult-place called "The Sunshade of Re-Horakhte" (P. Wilbour, A45,11 and S29 and 169). Like the Nephthys temple, these smaller shrines were considered affiliations or dependencies "within the House" (or primary temple enclosure) of Seth, who was supreme "Lord" of the town.

Sepermeru is perhaps of most interest to modern Egyptologists because of its status as one of the chief ancient Egyptian cult centers of Seth, along with the cities of Ombos, Nagada, and Avaris . It is thought that the cult of Seth waned considerably after Dynasty XX, due to the increasing "demonization" of this deity and his association with territories and priorities increasingly considered foreign to the general interests of Egypt. Religious and administrative prominence in Nome XIX was duly shifted south to Oxyrhynchus after this time (cf. te Velde, Seth: God of Confusion, p. 139). We know, however, that Seth continued to be the object of veneration in cult centers on the outskirts of Egypt well into Roman times, especially at Dakhlah Oasis, Kellis, Mut, Kharga, and Deir el- Haggar (cf. te velde, van Dijk, Essays, p. 236). It may be that Seth's cult survived in some form at Sepermeru, long after Sepermeru's decline as a religious center. Indeed, a late inscription in the Ptolemaic temple of Horus at Edfu makes reference to "Seth of Sepermeru," albeit with an insulting caveat that the god's canals in this district had become "dried-up and useless" (cf. P. Wilson, A Ptolemaic Lexikon, p. 827).

The foundations of both the Seth and Nephthys temples at Sepermeru were excavated and identified in the 1980s (cf. R. Lachaud, Les Deesses, p. 51). Therefore, the site is also of some interest for boasting remnants of the only surviving temple of Nephthys, along with her temple at Komir, near the ancient site of Esna.

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Sutekh (deity) - Temples
... metropolitan (yet provincial) locale of Sepermeru, especially during the Rammeside Period ... important temple called the "House of Seth, Lord of Sepermeru." One of the epithets of this town was "gateway to the desert," which fits well with Set's ... At Sepermeru, Set's temple enclosure included a small secondary shrine called "The House of Seth, Powerful-Is-His-Mighty-Arm," and Ramesses II himself ...