Jose Manuel Lopez, Antonio Pampliega and Angel Sastre entered Syria via southern Turkey on July 10th "and there has been no news of them since July 12th", said Elsa Gonzalez, president of the Federation of Press Associations of Spain.
"In that region there is intense fighting going on, so there is cause for concern," she said, but added: "For the moment we can only call it a disappearance."
Gonzalez did not know whether the three were working together, though Spanish national television station TVE said they were doing a joint investigative report.
Gonzalez told AFP she was informed of the situation by Spanish government officials.
"They cannot yet conclude that they have been kidnapped," she said.
The journalists' families called for "respect" and "the greatest possible discretion" in the case, in a statement quoted by various Spanish media.
Spain's foreign minister confirmed on Wednesday that Madrid is "fully active" in the search for the missing newsmen.
"Since hearing the news, we have been fully active" working to track down the three men, Jose Manuel Garcia-Margallo said during a public appearance in Madrid in comments quoted by Spanish media.
Garcia-Margallo said no demands had yet been received from any apparent
kidnappers and that his ministry was in "permanent contact" with its embassy in Turkey which was leading efforts to track down the men.
He said he had been in contact with various embassies and United Nations representatives in Spain as well as Spanish intelligence sources in Syria.
"I would ask that we proceed with discretion and respect" for those missing, he said.
The three journalists had worked recently for various media including Spanish newspapers La Razon and ABC, which was the first on Tuesday to report their disappearance.
Pampliega, a freelance war journalist born in 1982, contributed to AFP's text coverage of the civil war in Syria for a period up to 2013. He has also worked in countries such as Afghanistan, Irak, and Pakistan.
Lopez, born in 1971, is a prize-winning photographer who contributed images to AFP from several war zones, including from the Syrian conflict up until 2013.
According to data on the website of the Madrid Press Association, Sastre, 35, has worked in various trouble spots around the world for Spanish television, radio and press.
Dangers for media in Syria
Media rights group Reporters Without Borders ranks Syria as the most dangerous country in the world for journalists. It says at least 44 journalists have been killed there since the conflict broke out in 2011.
In August 2014, the jihadist group Islamic State decapitated US journalist James Foley, who was seized in northern Syria in 2012.
Three other Spanish journalists were kidnapped in 2013 while covering the conflict in Syria, where various armed factions are battling President Bashar Al-Assad's regime and each other.
El Mundo correspondent Javier Espinosa and freelance photographer Ricardo Garcia Vilanova were held by IS for about six months and freed in March 2014.
Earlier that same month another Spanish journalist, Marc Marginedas, a correspondent for the Catalan daily El Periodico, was also released after months in the hands of IS in Syria.
Espinosa said he and Vilanova were held along with 21 others including Foley in an industrial complex north of Aleppo.
Espinosa wrote in El Mundo that IS extremists staged mock executions of their Western captives.
Syria's conflict, which began in 2011 with anti-government protests, has degenerated into a civil war that has killed more than 230,000 people and displaced millions.
In the latest of countless massacres, on Tuesday a missile fired by Syrian forces killed at least 18 civilians in a residential neighbourhood of Aleppo, a monitoring group said.
Once Syria's commercial hub, Aleppo is divided between rebel groups entrenched in the east and government troops in the western neighbourhoods.
It has suffered devastating damage as each side tries to dislodge the other.
Rights groups have criticised both sides for indiscriminate attacks on civilians. In June 2014 Islamic State militants declared an "Islamic Caliphate" across territory they have seized in Iraq and Syria.