The EFL reported 112 positive tests from its strategic league-wide testing programme this week.
The testing programme involved 3,507 players and staff from 66 EFL clubs who are involved in FA Cup or league action this weekend. The six clubs who did not feature will be tested ahead of their next league fixtures.
It is understood almost a third of the positive tests centred on just three clubs, with most clubs averaging one or two cases.
The EFL moves to regular twice-weekly Covid-19 testing from next week, which is being funded by the Professional Footballers' Association.
The EFL's medical advisors Dr Richard Higgins and Dr Subhashis Basu added: "Today's results reflect the current speed at which the virus is spreading amid the emergence of a new variant of Covid-19, but the low reported numbers across the overwhelming majority of clubs mean we remain confident that our protocols continue to mitigate against the spread of infection as intended.
"The protocols, supported by the clubs and government, are allowing us to continue playing fixtures as scheduled but we cannot be complacent, which is why recently enhanced matchday and non-matchday Covid protocols have been issued to underpin the re-introduction of a league-wide testing programme which commences next week.
"Medical advice continues to support that following these protocols is the most successful route to mitigating against the spread of infection."
Southampton's FA Cup tie with Shrewsbury will not take place on Saturday after the Shrews notified the Football Association several players and staff members had tested positive for coronavirus, in addition to two positive tests last week - one confirmed as midfielder Marc Pugh.
Meanwhile, Blackpool's preparations for their FA Cup game against West Brom have been hindered by two positive tests in their weekly testing.
Wigan's League One fixture against Hull City has been postponed, with the club informing the EFL that it cannot fulfil the fixture due to a number of positive cases at the club, and Colchester United's League Two match against Tranmere has also been called off due to cases in both squads.
Krul confirmed as one of three Norwich cases
Norwich confirmed goalkeeper Tim Krul and Adam Idah are two of the three to test positive at the club, with an unnamed staff member the third.
The Canaries are the latest Championship side to experience positive results during this week's round of testing after Derby, Sheffield Wednesday and Middlesbrough also had their preparation for FA Cup ties impacted by coronavirus cases.
An official club statement read: "Norwich City can confirm that the club's latest round of Covid-19 testing across players and backroom staff has returned three positive results.
"Players and backroom staff were tested and results received over the early stages of this week. In line with Government, EFL and club protocols, all three individuals immediately began a period of self-isolation."
Championship leaders Norwich are set to host divisional rivals Coventry at Carrow Road in the FA Cup third round on Saturday, but will be without their goalkeeper.
Krul said on Twitter: "Earlier this week I was informed by the club that my Covid test came back positive. I immediately began my self-isolation period.
"I feel under the weather and fatigued. It's an important reminder to stay safe, this virus is not a hoax and to protect those around us."
Daniel Farke said: "They've been isolating for a few days because we tested at the beginning of the week. The most important thing is they feel well.
"Tim had some symptoms but it's not getting worse - more like a cold. It looks quite okay. They have a blocked nose or something so it's not too bad, but we take it seriously.
"Tim said how poorly you feel when you have it so stay disciplined and he's spot on. They were isolated from the moment after we took the tests so no reason to be majorly concerned."
Brentford boss Frank tests positive
Brentford manager Thomas Frank has tested positive for coronavirus, the Championship club have announced.
Frank, 47, was one of two individuals from the club to return a positive result after tests were conducted at the training ground on Thursday.
A club statement said: "Thomas will now isolate at home for 10 days under EFL and Government regulations.
"Due to medical confidentiality, we will not give any further details of the other positive test."
In Frank's absence, Brentford B head coach Neil MacFarlane led training on Friday and will be in charge for Saturday's FA Cup third-round tie against Middlesbrough.
News of Frank's positive test came three days after Brentford were beaten 2-0 by Tottenham in the Carabao Cup semi-finals.
Spurs boss Jose Mourinho confirmed on Friday that his entire squad have tested negative for coronavirus in the latest round of checks.
Derby youngsters test positive
Derby County have confirmed a "small number of individuals" who were due to travel to their FA Cup tie at Chorley have tested positive for Covid-19.
However, the Rams insist Saturday's third round tie will go ahead as planned.
Derby are sending a group of under-23 and under-18 players to Chorley following a coronavirus outbreak which has closed their training ground.
A club statement read: "Those that have tested positive for Covid-19, and their close contacts, will serve a period of self-isolation in line with UK Government guidelines.
"The Football Association, Public Health England and Chorley Football Club have been made aware of the situation and, at the present moment, Saturday's Third Round tie at Victory Park is due to go ahead as planned.
"Derby County would like to wish the individuals that have returned a positive COVID-19 test result a quick and safe return to full health."