Coach Mike Shanahan said Monday that neither player will require surgery, although both will sit out the final two games of the preseason.
An MRI revealed that two-time Pro Bowl linebacker Orakpo damaged some scar tissue in his left shoulder when he stretched his arm to try to tackle Chicago Bears receiver Devin Hester in Saturday night's game.
Orakpo had surgery on the same shoulder after tearing the pectoral muscle in the final game of last season. He thought he had torn the muscle again.
"I worked this hard trying to get back," Orakpo said. "And when I felt the pop, I thought it was done, to be honest with you. But it wasn't what we thought."
Meriweather, signed in the offseason to fill the vacant starting strong safety spot, hurt his left knee when a player fell on him during a touchdown run by Michael Bush. Shanahan said Meriweather's knee was sore and swollen, but the MRI revealed no major damage.
Also Monday, linebacker London Fletcher returned to practice after missing Saturday's game and multiple practices last week. Shanahan and Fletcher both said the defensive captain wasn't feeling well but declined to elaborate.
Shanahan said running back Roy Helu Jr. now has soreness in both Achilles. Helu had been limited with tendinitis in his left Achilles, slowing his bid for the starting job. He missed Saturday's game and did not practice Monday.