They suffer from long days alone and get less holiday.
Two thirds struggle with their mental health, against the overall average of one in six, while nine in ten feel lonely, the Mercedes-Benz Vans poll shows.
A third have fewer than three conversations a day, spending up to 25 hours a week alone.
But football pundit Chris Kamara is launching Vantasy Football, a tournament bringing drivers together at St George’s Park near Burton, Staffs. Drivers can sign up online.
Paul Murphy, a healthcare company driver, said: “Sometimes you feel like you’re living in your own head with no one else, particularly those on longer routes who only have a few conversations every day.
“Without talking, a small problem can fester.”
It comes as businesses try to meet growing demand for round-the-clock home deliveries fuelled by online sales from platforms like TikTok shop, Vinted and Depop.
There has been a 37 per cent rise in van drivers on UK roads since 2012 and some 49 per cent of business leaders say they will have to rely more heavily on van drivers in the coming months.
More than half of van drivers also spend over 50 hours per working week on the road, compared with the national average of 36.4.
A separate poll for travel company TUI also found that white van men typically got 12 days less holiday a year than 9-to-5 workers.
Ex-Sky Sports pundit Chris, 66, called van drivers the “backbone of society”, adding: “From couriers delivering our online shopping to the ambulances that support our NHS, drivers across the country make sure that we are moving as a nation.
“We need to make sure that all of our van drivers are healthy and happy at work.”
He continued: “Spending time on your own, not talking to people, these things have a real impact on mental health.
“The camaraderie of sport is such a great way to overcome loneliness.”