The 20-year-old has played 34 one-day internationals for Pakistan and was included in their 15-man squad for the May 30-July 14 World Cup in England and Wales.
The 1992 champions will play a lone Twenty20 international and five ODIs on their tour of England, which begins on May 5.
"Wrist spinner Shadab Khan has been ruled out of the series against England after tests revealed a virus that will require treatment and rest for, at least, four weeks," the Pakistan Cricket Board said in a statement.
The board said it would set up appointments with specialists in England to help Shadab, who is also a useful lower-order batsman, recover in time for Pakistan's World Cup opener against West Indies on May 31.
All teams are allowed to make changes to their World Cup squads until May 23. Pakistan selectors have already put batsman Asif Ali and seamer Mohammad Amir on standby should they have to make changes to their squad.
(Reporting by Sudipto Ganguly in Mumbai; editing by Peter Rutherford)
