The blizzard warning, "the first issued by this office," is scheduled to begin at 4 a.m. Friday and remain in effect until 4 p.m. Saturday, the National Weather Service San Diego said in a tweet.
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Travel is expected to be "very difficult to impossible" in the area, the agency said, adding that hazardous conditions will impact the morning and evening commute. "Visibility will be near zero."
The San Bernardino County alert comes on the heels of a similarly rare blizzard warning that was issued earlier this week for the mountains of Los Angeles and Ventura counties, also from 4 a.m. Friday to 4 p.m. Saturday.
Forecasters said up to 5 feet of snow could accumulate in the mountains above 4,000 feet, accompanied by wind gusts topping 80 mph. Higher elevations could see as much as 8 feet of snow, with accumulations of 6 to 12 inches possible at elevations between 2,000 and 4,000 feet, "including most major mountain passes."
"Travel should be restricted to emergencies only," according to the National Weather Service. "If you must travel, have a winter survival kit with you. If you get stranded, stay with your vehicle."
Kyle Takata, a resident of Orange, visited the snow-covered San Bernardino Mountains on Thursday.
SoCal cold storm timeline: Here's when to expect rain and snow in your area
"This is nothing short of awesome," he said in a roadside interview near Highland as snowflakes fell on his jacket. "This is the first time I've seen something like this, so it's really cool."
Although Takata's SUV was equipped with all-wheel drive, he decided that putting snow chains on this tires was the safe thing to do.
"We're going to be snowboarding all day," he said. "Now's the best time to it."
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Meanwhile, a semitrailer jackknifed on Highway 330, south of Running Springs, prompting the closure of the highway. Earlier in the morning, Caltrans snow plows worked to keep the highway as clear as possible.
Overnight Wednesday, a multi-vehicle crash on Highway 189 near Crestline. More than a dozen vehicles were involved in the chain-reaction pileup.