His long-planned Middle East tour comes amid an outbreak of Israeli-Palestinian violence.
After a visit to Cairo, the head of American diplomacy, Antony Blinken, is expected in Jerusalem on Monday then in Ramallah, in the occupied West Bank, the next day.
The subject of tensions will probably be, from this Monday, at the heart of the discussions in Egypt, where the American must meet with President Abdel Fattah al-Sissi and his Minister of Foreign Affairs, Sameh Choukri.
Cairo historically plays an intermediary role between Israel and Palestine.
“Measures for de-escalation”
The arrival of Antony Blinken in Israel then in the West Bank comes after several bloody days.
Last Thursday, an Israeli raid - the deadliest in years - left nine dead on the Palestinian side in Jenin, in the West Bank.
The next day, a Palestinian shot and killed seven people in East Jerusalem before being shot.
That same day, the Israeli army bombarded the Gaza Strip in response to rocket fire from this enclave which it maintains under blockade.
On Saturday, a Palestinian shot and wounded two Israelis also in East Jerusalem, the eastern part occupied by Israel.
On Sunday, Israeli guards killed a Palestinian in the West Bank, Palestinian territory occupied since 1967 by Israel.
Jerusalem: 13-year-old boy injures two Israelis in shooting
Washington has already condemned the "appalling" attack in East Jerusalem.
According to the State Department, Antony Blinken will urge Israeli Prime Minister Benjamin Netanyahu and Palestinian President Mahmoud Abbas to “take urgent steps towards de-escalation”.
In Israel, he will also insist on "the importance of maintaining the historic status quo" on the esplanade of the Mosques in East Jerusalem, a hotbed of tension between Israelis and Palestinians.
This site is the third holiest in Islam and the holiest in Judaism.
The Abraham Accords, a process of normalization between Israel and several Arab countries, should also be on the menu of discussions, Benjamin Netanyahu cherishing the hope of rallying Saudi Arabia to it.
“The conversation with Mahmoud Abbas is not going to be pleasant”
But the head of American diplomacy's room for maneuver seems quite limited.
Experts interviewed by AFP do not expect significant breakthroughs, the United States will probably be content to hammer home their support for the two-state solution, Israeli and Palestinian.
“The best they can get is for things to stabilize in order to avoid a repeat of May 2021”, the last war between Israel and the Palestinian armed groups, assures Aaron David Miller, expert at the Carnegie Foundation for the Washington international peace.
For Ghaith Al-Omari, an expert from the Washington Institute, “this visit does not signal any change in the American position with regard to the Israeli-Palestinian conflict” but “the conversation (with Mahmoud Abbas) is not going to be pleasant”.
Antony Blinken's visit to Israel reflects Washington's desire to reconnect with Benjamin Netanyahu, head of the most right-wing government in Israel's history.
It comes after that of the National Security Advisor of the White House, Jake Sullivan.
CIA Director William Burns recently visited the region, including Cairo.