Thirty people were reported killed at Hilton Hotel in the Egyptian resort town of Taba in the Sinai desert close to the border with Israel, where many Israelis were vacationing at the close of a Jewish holiday.
Two other blasts also occurred about two hours later in nearby resort towns of Ras al-Sultan and Nueiba, witnesses said on state television.
Seven Egyptian workers were killed in the attack at Ras al-Sultan, the channel said quoting Egyptian police.
Security sources said there was growing conviction that the blast at Hilton had been caused by a truck laden with explosives.
A foreign ministry spokesman said Israel will help evacuate any of the 12,000-15,000 Israelis who wish to leave Sinai in the wake of the explosions.
An Israeli official at the border, Itzik Chai, told Channel 2 that "the situation is chaotic with fears of more explosions taking place. The Egyptians did not immediately allow Israeli rescue workers to move inside due to some bureaucratic delay."
Israel flew doctors from all over the country to treat the injured and helicopters were ferrying them to the Soroka Medical Center in Be'er Sheva. Many of the injured were taken to the Yoseftal hospital in Eilat.
"I heard a huge explosion. The wall near me collapsed and people began to run. There were many casualties...the explosion was outside. When we went out we saw the shops and the internal wall of the hotel had collapsed," a witness told Army Radio.
"Some people said it was a gas canister explosion and others said it was a terrorist attack. There are a lot of people lying on the ground. There is a lot of blood, a lot of screaming," he added.
Resorts dotted along the Sinai's desert coast have remained popular holiday spots for Israelis since the territory was handed back to Egypt as part of a 1979 peace deal.
The town of Taba, next to the Israeli resort of Eilat, was handed back to Egypt only in 1989 after years of wrangling.