"Make no mistake, this is an intentional act of terrorism," Akil Davis, the head of the FBI's Los Angeles field office told reporters near the site of the fatal explosion.
"This is probably one of the largest bombing investigations that we've had in southern California," he added.
He confirmed that one person near the clinic at the time of blast had been killed and that four others were wounded. Work was ongoing to identify the deceased, he added.
In response to a reporter's question on whether the clinic in Palm Springs was deliberately targeted, Davis answered: "We believe so, yes."
The city's mayor, Ron deHarte had earlier told AFP that investigators confirmed a bomb exploded in or near a vehicle outside the clinic.
Eyewitnesses told local media they had seen human remains near the American Reproductive Centers clinic, with aerial footage of the scene showing the building roof had collapsed.
- Debris for 'several blocks' -
The charred remnants of a vehicle lay in a parking lot, some distance from the apparent epicenter of the explosion.
Debris was blown straight through the building and scattered across the road, while the roofs of a number of nearby buildings had been damaged, indicating the intense force of the blast.
Davis of the FBI described the explosion as "significant" and said debris had been thrown more than two hundred yards (180 meters) from the scene, but declined to comment further on the characteristics of the bomb.
The local ABC affiliate, which cited an unnamed law enforcement source, said the person who died was a suspect in the blast.
Davis told reporters that though the FBI was working to identify the deceased, "we are keeping that close hold in order to protect the integrity of the investigation."
A statement posted on social media by the clinic said no staff had been hurt, and that its lab -- "including all eggs, embryos, and reproductive materials -- remains fully secure and undamaged."
It said that "a vehicle exploded in the parking lot near our building."
Reproductive care, including abortion and fertility services, remains controversial in the United States, where some conservatives believe the procedures should be outlawed for religious reasons.
Violence against clinics providing such services is rare, but not unheard of.
President Donald Trump's Attorney General Pam Bondi said federal agents were working to determine exactly what had happened.
- 'Unforgivable' -
"But let me be clear: the Trump administration understands that women and mothers are the heartbeat of America. Violence against a fertility clinic is unforgivable," she said in a statement on social media.
People living near the clinic reported feeling the shaking from the blast throughout the city.
Matt Spencer, who lives in a nearby apartment complex, told the Palm Springs Post he ran outside as soon as he heard the blast, and was confronted with the sight of the burned out car and what appeared to be a body in the middle of the road.
"In front of the building [the car] was blown clear across four lanes into the parking lot of [Desert Regional Medical Center]," he told the paper.
"I could see the back of the car still on fire and the rims, that was the only thing that distinguished it as a car."
California Governor Gavin Newsom had been briefed on the explosion, his office said.
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© Agence France-Presse
