An apparent reduction in the performance of neonicotinoid seed treatments in controlling thrips, especially in cotton, has been observed, which has coincided with the increased use of both pre- and post-emergence herbicides to control glyphosate-resistant weeds. The objective of this research was to evaluate the potential interactions of both pre- and post-emergence herbicides on the efficacy of insecticide and fungicide seed treatments in cotton Aldicarb along with imidacloprid and thiamethoxam seed treatments reduced thrips numbers compared with non-treated seed. However, thiamethoxam did not provide effective control. Some pre-emergence herbicide treatments reduced plant health. While there was evidence that thrips injury and herbicides could both negatively affect plant health, there was little indication of interactions between these factors, indicating that the efficacy of thrips treatments was the primary factor affecting yield. Fungicide seed treatments also generally improved seedling health and improved stand density in all tests. In these tests, negative effects of pre-emergence herbicides on plant health were also observed, but these data indicated no interaction with fungicide seed treatments. Tests were also conducted to determine the potential interaction of insecticide seed treatments and post-emergence herbicides. In 2013, applications of glufosinate or glufosinate plus s-metolachlor caused substantial plant injury as evidenced by low vigor ratings, decreased plant biomass and height, and yield. While there was clear evidence that thrips and postemergence herbicides, especially glufosinate, negatively affected plant health, there was little evidence of interactions between these two factors. The role of microbial decay in the diminishing activity of neonicotinoid insecticides use as seed treatment was also tested. Sterilizing the soil reduced the concentrations of the imidacloprid and thiamethoxam metabolites indicating that soil microbes can degrade both insecticides. However, the amounts of degradation to secondary metabolites were relatively low, and it is unlikely that microbial metabolism of either insecticide would appreciably impact their performance as seed treatments. Collectively, these data indicate the negative impacts of thrips, seedling disease and herbicide injury would be additive. Using herbicides at recommended rates and according to label restriction should reduce the risk of compounding the effects of thrips or seedling disease with herbicide injury.