The explosion Sunday morning -- in the city's Abbassiya district -- hit the small church of St. Peter and St. Paul attached to the St. Mark's Coptic Orthodox Cathedral, said the Coptic Church's official spokesperson, Rev. Paul Halim, according to the government-sponsored Al-Ahram news outlet.
At least 25 people are dead and dozens injured, Al-Ahram said, citing the health ministry.
Egyptian state news agency MENA reported, citing security sources, said a 12-kilogram TNT bomb caused the blast..
In response to questions from CNN about the size of the bomb, a police official who asked not to be named told CNN: "It is too early to determine the type and amount of the explosives used," and authorities are unable to confirm reports about a 12-kilogram bomb.
No claim of responsibility
The attack targeted one of the most symbolic religious sites for Copts, an ethno-religious group centered in Egypt. The Coptic Orthodox Church released a statement on its Facebook page, saying in part:
"As we are bereaved by this violence and terrorism that attacks worshipers, we pray for these martyrs and for the wounded. The Egyptian church stresses on persevering national unity that keeps all Egyptians on Egypt's blessed land."
Video from the scene shows shards of glass and other debris scattered across the chapel's floor. Patches of blood cover some of the wooden pews.
There has been no immediate claim of responsibility for the attack.
A militant group responsible for a string of deadly attacks targeting Egyptian security forces condemned the bombing.
"Our prophet had taught us even while we fight not to kill a child nor woman nor old person nor worshiper in his place of worship," the Harakat Sawa'd Misr, or Hasam Movement, said in a statement on its Facebook page.
President Abdel Fattah El Sisi condemned the attack and declared a three-day period of national mourning.
The Grand Mufti, the highest official of religious law in Egypt, condemned the "deplorable terrorist attack" on the cathedral.
"Attacking churches whether by demolition, bombing, killing those inside, or terrifying ... secure people are prohibited in Islamic Sharia," Sheikh Shawky Ibrahim Abdel-Karim Allam said.
He called for unity against "black terrorism that tries to instigate sectarianism and sedition among the two wings of Egypt -- Muslims and Christians -- in a bid to weaken the nation."
The Grand Mufti also extended his condolences to Pope Tawadros ll of the Coptic Orthodox Church of Alexandria.
Hundreds of demonstrators gathered outside the cathedral Sunday to voice their anger at police and some pro-government television anchors, according to Al-Ahram.
They called for the resignation of the interior minister, Magdy Abdel Ghaffar.
Protesters chanted: "This time won't pass, even if we all die. ... This is not sectarian strife, let's get the world to hear."
Sunday's explosion came just two days after two bombs killed
six police officers and a civilian in Giza's Haram district, on the street leading to the city's famed pyramids.
Copts facing persecution
Copts face persecution and discrimination that has spiked since the toppling of Hosni Mubarak's regime in 2011. Dozens have been killed in sectarian clashes. There is also little Christian representation in Egypt's government.
Coptic Christians make up about 10 percent of Egypt's 91 million residents. They base their theology on the teachings of the Apostle Mark, who introduced Christianity to Egypt, according to St. Takla Church in Alexandria, the capital of Coptic Christianity.