Severe weather warnings of more than 10cm (4in) of snow have been issued by the Met Office for 26 December.
It said rain, sleet and snow are set to spread east across parts of Northern Ireland, England and Wales, before clearing in the evening and overnight.
Forecasters said there was a risk of several centimetres of snow even at low levels, and roads could turn very icy.
The yellow warning - meaning "be aware" - is in place from 11:00 GMT on Friday until 06:00 on Saturday.
The Met Office said a depression developing over the Atlantic was expected to track east and then south-eastwards across the southern half of Britain during Friday.
Snow is expected to the north of this depression, and heavy rain to the south.
The Met Office said: "There remains much more uncertainty than average regarding the track of this depression which in turn leads to uncertainty about the location of the heaviest precipitation and how much snow there will be.
"Where snow does occur, accumulations of 2cm to 4cm are likely even to lower levels and in excess of 10cm possible."
BBC weather presenter Nina Ridge said: "Our main concern is what's approaching from the south-west of England on Boxing Day.
"To begin with, we'll see some wet and windy weather for the South West but it's as that bumps into the colder conditions and as the intensity increases that we could see this spell of sleet and snow."
Forecasters have also warned of freezing temperatures in the days leading up to New Year.
The Met Office said there was an 80% chance that conditions could "increase the health risks to vulnerable patients and disrupt the delivery of services".
Earlier, Christmas travellers were warned to be prepared for ice and snow across large areas of Scotland.
The Met Office issued warnings of ice developing on Christmas morning after showers and snow and sleet on 26 December.
The cold snap is expected to affect the north-east initially before spreading south.