The Silkmen had taken the lead through George Donnelly before Michael Jacobs, Luke Guttridge and Adebayo Akinfenwa put the Cobblers ahead. A late Ben Tomlinson goal gave Macclesfield hope of salvaging a draw but ultimately it was not enough.
Simpson was without midfield trio Dwayne Mattis (ankle), Ross Draper (broken metatarsal) and Lewis Chalmers (hernia) along with defender Paul Morgan (ankle) for the game and he revealed his fear of losing more players to injury.
"We must be jinxed, that's 13 players on the injured list now and you can't play without players," he said. "I spent five hours on the phone last (Monday) night trying to get players in for the game."
"We only trained for 10 minutes yesterday (Monday) because I was frightened to death that we'd lose another player! Everything is going against us at the moment but we've just got to keep working hard and hope our luck changes."
"I'm gutted for the players, they've giving everything and I thought we might win it at one stage. We played well enough to get something out of the game but some of the players are a bit rusty."