Lewis lasted three snaps in his season debut before re-aggravating a left calf strain.
Lewis originally injured the calf during warm-ups prior to the second preseason game against the New York Jets Aug. 17. He suffered a setback during practice in the week leading up to the regular-season opener against Kansas City.
Lewis had missed three games in his entire career with the Jaguars and now will be out indefinitely.
Clay Harbor is next up at the position but with Blaine Gabbert at QB it seems like downgrades are necessary for all Jacksonville receivers.