Palicki, 31, and Blood, 33, already star on the current second season of the show as Bobbi Morse and Lance Hunter, respectively.
Giving the spin-off a "Mr & Mrs Smith" vibe, Lance and Bobbi are former husband and wife, who have let sparks fly in a push-pull relationship on "Agents of S.H.I.E.L.D", reported Deadline.
Producer Marvel, ABC network and representatives for Palicki and Blood declined comment.
The spin-off is supposed to be set up by events from this season of "S.H.I.E.L.D."
The offshoot was developed by "S.H.I.E.L.D." executive producer Jeffrey Bell and co-executive producer Paul Zbyszewski, who are writing the script and would executive produce.
ABC is not expected to make a formal greenlight call until the script comes in, with the hope being to be able to do that before the upfronts. The spin-off may film a promo or do a pilot.