The Met Office has issued a severe weather warning for snow across the region throughout tomorrow and into Monday, with the biggest accumulations settling on higher ground.
More than 10cm could fall at lower levels and travel disruption should be expected, it said.
The north of England is expected to see some of the worst conditions along with the north-west and the Midlands.
Met Office chief forecaster Eddy Carroll said: “Even at this short timescale there is currently a lot of uncertainty about the extent of the rain, sleet and snow later this weekend.
“People should stay up-to-date with the latest forecasts and warnings and be prepared for some disruption to travel.”
The weather warning – a yellow alert, urging residents to be aware – could be upgraded to amber as a clearer picture of the conditions emerges, he said.
Steve Crosthwaite, of the Highways Agency, said: “We would advise road users to stay alert to the possibility of severe weather and to check the latest forecast before their journey.
“Anyone setting off on Saturday for a weekend away perhaps should be prepared for more difficult conditions on the way home and commuters would be well-advised to check Sunday evening and be prepared to allow extra time for their journey to work on Monday morning.
“We have been working solidly throughout the winter to treat our network. Our 500-strong fleet of snowploughs and gritters, plus our traffic officer patrols, will be doing everything they can to keep traffic moving.”
It will be a cold, frosty and icy start for many on Monday with further outbreaks of sleet and snow, particularly in northern and eastern parts of the UK.
Conditions will gradually improve through the day but it will remain cold.
The latest snow warning comes a fortnight after blizzards brought days of disruption to schools, airports and traffic networks across the UK. Wildlife experts have warned that the return of wintry weather could put the brakes on the first signs of spring, which had just begun to appear, coaxed by last week’s warmer temperatures.
The mild weather saw a surge in reports of snowdrops, elder buds, hazel flowering and frogspawn submitted to the Woodland Trust’s Nature’s Calendar scheme, which collects signs of the changing seasons spotted by the public.
The trust said it had received 199 snowdrop sightings, 30 of elder budburst, 97 of hazel catkins flowering and 23 sightings of frogspawn so far, as well as anecdotal information from regional staff of wild garlic blossoming in Devon and hawthorn in leaf in Taunton.
But with the latest cold spell sweeping in, the trust said trees and plants could halt their development and some species fooled by early warm weather such as insects which emerge and cannot return to shelter, could be hit.
Frogs breed only once a year, and if spawn already laid freezes, the breeding effort will be wasted, according to Dr Kate Lewthwaite, of the trust.
But really cold weather in April or very mild weather early in January tended to be more damaging for wildlife than the current changeable conditions, she said.