Already without their second-leading scorer and a second starter due to injuries, Poplar Bluff junior Jordynn Caldwell took a knee to the back and headed to the bench in the 42nd minute Friday.
Five minutes later, the Mules lost their lead and Farmington got a late goal to win 2-1 at Mules Stadium.
"When Jo went down that was huge," Mules coach Rusty Crafton said.
Poplar Bluff (6-9) was without Neida Grimaldo, who scored six goals in 11 games before a shoulder injury, and freshman Brylee Misner, out with a foot injury. Shelbey Johnson had a cast on her left hand after breaking a bone in a non-soccer related fall.
Johnson put the Mules ahead with her 28th goal of the season in the eighth minute. Lauren Rowland, Poplar Bluff's lone senior honored before the game, assisted on the play.
Riley Turner scored both goals for the Knights (7-7).
"We fought for what we got," Crafton said. "...We've got girls playing different positions, they're going to have to step up. That's all there is to it."
Ady Kingree moved into Misner's spot in the back as fellow freshman Kiley Bess, who recently returned from an ankle injury suffered during the basketball season, has taken over for Grimaldo in the midfield.
Only eight players have started every game, including keeper Shelby Sievers, who made it back in time after throwing the shot and discus in Sikeston to make 11 saves. The junior won the conference title in the discus and was second in the shot.
Sievers kept the Mules ahead with a punch save on a corner by the Knights in the 46th minute but Turner scored on a break off a pass from Emily Greif a minute later.
Turner had another break in the 75th minute but LeeAnn Coffee broke it up and Audrey Cisne was able to clear.
With just over two minutes left, Meghan Burcham's pass put Turner on another break when the ball deflected off the defender's feet to Turner as the two met. Turner avoided another defender to get off a shot from 20 yards that slipped into the net past the outstretched reach of Sievers.
"I thought defense stepped up," Crafton said. "For Jo, our leader in the back, going out, I thought Addy Kingree stepped up and played good. We might have to keep her there for awhile, play a little more defensive."
The Mules out-shot Farmington 23-15, but keeper Rachel Turner stopped Johnson on a break twice in the second half and also sat on a long shot from Lauren Rowland.
Turner initially stopped Johnson's shot in the eighth minute but it trickled over the goal line. Rowland's second assist of the season came when Johnson was able to beat her defender in the box to get off a shot.
Rowland nearly had another assist in the 35th minute when her cross from the right side was headed by Jayla Matlock. Emily Nelson and the Farmington keeper scrambled after the loose ball with Nelson getting a foot on it, sending it inches past the far post and just out of the reach Matlock.
Poplar Bluff had two more good scoring chances midway through the second half and were later caught offside twice.
"We just couldn't capitalize on our opportunities," Crafton said.
The Mules have now lost five one-goal games in which they either led or were tied at halftime. They travel Tuesday to Liberty-Mountain View before hosting Perryville on Wednesday.
Poplar Bluff won the junior varsity game 3-1 with goals from Valeria Palma-Ramirez, Savannah Hicks and Nelson.