The spread of mechanical cotton harvesting can cause significant changes in the conventional cotton production process from the point of planting pattern and variety. A field experiment was conducted to evaluate the cotton picker and stripper performance as affected by in conjunction with plant density and cultivar from 2019 to 2020. The experimental design was a randomized complete block with split-split plot arranged in three replications. The cotton harvester were in two levels of spindle picker cotton (PC) and finger stripper cotton (SC) as the main plot, three cultivars as the subplot include: Macsa (V1), Golestan (V2), Hekmat (V3) and the plant density (PP1:10, PP2:13, PP3:16 plant m2) as sub-sub plot. The results showed that cotton harvester, variety and plant density had a significant effect on performance indexes of cotton harvester. The maximum effective field capacity and material capacity belonged to finger stripper harvester. The results also revealed that the PC treatment on average decreased ground loss by 38.9% and increased harvesting efficiency by 3.5% compared to SC treatment. As the plant density was increased from 10 to 16 plant m2 in SC treatment, the ground loss and stalk loss were decreased (22.3 and 50.5, respectively). The highest seed cotton yield was observed in the V2× PP2 interaction. According to our findings and based on the seed cotton yield and crop losses, application of PP2 treatment in combination with V2 and V1 treatments were seen suitable in the cotton growing regions of Fars province.