Guterres, who is currently in Brussels, will arrive in Egypt on Friday evening for "his annual Ramadan solidarity trip which comes this year in turbulent times, with the conflict in Gaza," spokesman Farhan Haq said.
While there, the secretary-general will meet aid workers on the Egyptian side of Rafah, which is split over the border with the Gaza Strip and has been a key gateway for humanitarian supplies reaching the territory.
Guterres will also visit a hospital in El-Arish, an Egyptian city which sits close to the Gaza border.
Israel this week threatened to launch an offensive on the Palestinian side of Rafah, which US Secretary State Antony Blinken has warned would be a "mistake" that "risks further isolating Israel around the world."
Around 1.5 million people are crowded into Rafah, Gaza's southernmost city, after almost six months of Israeli bombardment that has brought the territory to its knees.
At least 31,988 people have been killed in Gaza since the start of Israel's offensive in October, according to the Hamas-led health ministry in Gaza.
During his visit, Guterres -- who last visited Rafah in October -- will "reiterate his calls for a humanitarian ceasefire and silencing the guns, particularly in Gaza and Sudan," Haq said.
In Cairo he is expected to have iftar -- an evening meal marking the end of Ramadan's daily fast -- with refugees who fled Sudan because of ongoing conflict there.
Guterres will then travel to Amman in Jordan to visit UNRWA facilities.
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