Mackie, who tops the Argyle scoring charts with five goals along with on-loan Blackburn winger Alan Judge, is suffering with sickness and has not flown north with Paul Mariner's squad.
Mackie was partnered with Kiwi striker Rory Fallon when Argyle drew 0-0 with Newcastle in the first game on Saturday January 2.
Mariner has the option of calling upon Alan Gow, Ashley Barnes or teenager Joe Mason, all strikers and unused substitutes at Home Park.
Central defender Kari Arnason (leg) is an injury doubt while midfielder Jim Patterson is still ruled out by a hamstring injury.
Winger Yala Bolasie has returned from his loan spell at League Two Barnet but is cup-tied.