The PA news agency understands Chilwell has returned to Chelsea for assessment on a pre-existing injury, while Atletico Madrid defender Trippier departed due to a personal matter.
Trippier captained England in their 3-0 friendly win over Wales last week and also started the 2-1 victory against Belgium.
Chilwell did not feature in either match having breached Covid-19 guidelines when he reportedly attended a surprise birthday party for club-mate Tammy Abraham last weekend.
An update from the camp as the #ThreeLions continue preparations for Denmark:
— England (@England) October 13, 2020
Gareth Southgate still has a 28-man squad to select from for the game against Denmark – although his options on the left-side of the pitch are now drastically reduced.
Chilwell would have been seen as the obvious player to slot in at either left-back or left wing-back, a position Trippier occupied in the Belgium win on Sunday.
With both missing, it is likely Southgate will turn to one of two Arsenal players at his disposal – with Bukayo Saka and Ainsley Maitland-Niles both adept down the left.
Captain Harry Kane is expected to be fit to start having come on as a second-half substitute at the weekend as England go in search of the win that will leave qualification to the Nations League finals in their own hands.