Some 31% of drivers - equivalent to 10.5 million - will be using a car for an overnight trip, the RAC poll indicated.
From Saturday, people in England will be permitted to spend the night away from their home for the first time in more than three months.
The RAC survey of 1,400 drivers suggested that this weekend 11% will stay over at a family member's home, 8% will be at a friend's home and 6% will go camping.
A further 6% will either spend the weekend at a caravan site, in self-catered accommodation or at a hotel, bed and breakfast or second home.
RAC Breakdown spokesman Rod Dennis said: "These figures suggest that after 15 weeks of lockdown, a large proportion of drivers in England are desperate to reconnect with friends, family and indeed nature by staying overnight, be that in a house or on a camping or caravan site.
"This could lead to some busy conditions on the roads, with the location of queues likely to be dependent on just how far people travel.
"Motorways and major A-roads could end up taking the brunt of the traffic if people have longer distances to drive to see family and friends or to take a weekend break.
"While our research suggests weekend traffic could be the heaviest of the year so far, a breakdown has the potential to make matters even worse."
The RAC advised motorists to carry out a series of checks before hitting the road, including tyre condition and pressure, and oil and coolant levels.