Technical Abstract: Seed from Upland cotton, Gossypium hirsutum L., provides a desirable and important nutrition profile. In this study, six seed traits (protein content, oil content, seed hull fiber content, seed index, seed volume, embryo percentage) for F3 hybrids of 13 cotton chromosome substitution lines crossed with five elite cultivars over four environments were evaluated. Oil and protein were expressed both as percentage of total seed weight and as an index which is the grams of product/100 seed. An additive and dominance (AD) genetic model with cytoplasmic effects was designed, assessed by simulations, and employed to analyze these seed traits. Simulated results showed that this model was sufficient for analyzing the data structure with F3 and parents in multiple environments without replications. Significant cytoplasmic effects were detected for seed oil content, oil index, seed index, seed volume, and seed embryo percentage. Additive effects were significant for protein content, fiber content, protein index, oil index, fiber index, seed index, seed volume, and embryo percentage. Dominance effects were significant for oil content, oil index, seed index, and seed volume. Cytoplasmic and additive effects for parents and dominance effects in homozygous and heterozygous forms were predicted. Favorable genetic effects were predicted in this study and the results provided evidence that these seed traits can be genetically improved. In addition, chromosome associations with additive and dominance effects were detected and discussed in this study.