An improved understanding of crop stress from multiple pests is needed for better implementation of integrated pest management (IPM) strategies. Field studies were conducted in 2003 and 2004 at two locations in eastern Nebraska to describe the effects of simulated early-season insect defoliation of soybean and duration of weed interference on soybean growth. Three levels of simulated defoliation (undefoliated, 30, and 60%) and seven durations of weed interference (weedy and weed free; weed removal at V2, V4, V6, R3, and R5) were evaluated in a split-plot design. Defoliation significantly reduced soybean leaf-area index (LAI), total dry matter (TDM), and crop height in season-long weedy treatments only. Biomass partitioning during vegetative and reproductive growth was affected by both defoliation and weed interference. Increase in soybean relative growth rate (RGR) and biomass production soon after defoliation occurred (e.g., V5 stage) indicated potential defense mechanism by which soybean is able to adjust its physiology in response to the loss of leaf area. Weed interference combined with defoliation caused the greatest yield losses up to 97%. Results from this study indicate the need for monitoring early-season insect density and weed growth to determine if simultaneous control of both pests may be needed.