Police are yet to provide official information on the death toll of the accident, which happened around 2 PM and involved some 70 vehicles, including a bus and several lorries, according to local firefighters.
Several media reports suggest up to five people may have been killed and scores injured in the pile-up near the Senožeče exit, some 40 kilometres northeast of Koper.
Anže Kristan, the head of the emergency ward at UKC Ljubljana, told POP TV seven injured people had already arrived at the hospital, with several more on the way.
The cause of the accident is believed to be thick fog, which is still lingering, hampering the rescue operation.
Eyewitness photos published by online media such as www.slovenskenovice.si and www.24ur.com showed dozens of crumpled cars, some of them lodged under lorries.
TV broadcasts from the scene show a massive rescue effort still under way more than four hours after the crash, with dozens of firefighters, paramedics and police helping survivors.
Police are expected to release preliminary official information once the rescue effort is completed.
If the death toll is confirmed, this would be the deadliest pile-up in Slovenian history. It is already the biggest in terms of the number of vehicles involved.