JD Wetherspoon has seen 66 positive Covid-19 test results among its 41,564 employees across 861 pubs in the 10 weeks since 4 July.
The pub giant said 811 pubs have reported zero positive tests, 40 pubs have reported one, six pubs two, two pubs three and two pubs four, as it disputed reports that spikes in cases could be linked to hospitality venues.
It added that most of the reported cases have been mild or asymptomatic and 28 of the 66 employees have already returned to work, after self-isolating.
Chairman Tim Martin said: "It is clearly not the case that pubs are ‘dangerous places to be'.
"There have been more positive cases at one farm in Hereford than at all Wetherspoon pubs – and over four times as many at one sandwich-making facility in Northampton.
"As Swedish epidemiologist Johan Giesecke has said, strong scientific evidence shows that handwashing and social distancing, as practised by most pubs, work.
"In this connection, Wetherspoon has invested around £15m on comprehensive social distancing and hygiene measures. These include reducing capacity, spacing out tables, the installation of screens between tables and around tills, and an average of 10 hand sanitisers per pub."
He added: "If pubs are closed, or restricted so much that they become unprofitable, a great deal of the strenuous effort of the hospitality industry's 3.2 million employees, currently engaged on upholding hygiene and social distancing standards, will be lost – leaving the public to socialise at home or elsewhere, in unsupervised circumstances."