Southern Root-Knot nematode and common cocklebur interfere with cotton growth and yield. A greater understanding of the interaction of these pests with cotton growth and yield is needed for effective integrated pest management (IPM). An additive design was used in outdoor microplots with five common cocklebur densities (0, 1, 2, 4, and 8 plants per plot) growing in competition with cotton, with and without the presence of southern Root-Knot nematode. Differences in cotton height could not be detected among common cocklebur densities or nematode presence at 3 wk after transplanting (WAT); however, differences in crop height were observed at 5 WAT between nematode treatments. In the absence of nematodes, the relationship between cotton yield loss and common cocklebur density was described by a rectangular hyperbolic regression model (P < 0.0001). Maximum yield loss from common cocklebur in the absence of nematodes exceeded 80%. In the presence of nematodes, there was a linear relationship between cotton yield loss and common cocklebur density (P = 0.0506). The presence of nematodes at each common cocklebur density increased cotton yield loss 15 to 35%. Common cocklebur plant biomass was 25% greater in nematode treatments, likely because of the reduced competitiveness of the cotton plants in these plots. This study demonstrates that multiple pests can interact to cause an additive reduction in crop yield.