A study was conducted to evaluate various substitutions of cotton burr and linters from cotton gin waste (CGW) as natural fiber reinforcements in ligno-cellulosic polymer composites (LCPC). Samples were fabricated with approximately 50 percent natural fiber, 40 percent high-density polyethylene, 4 percent mineral filler, and 6 percent lubricant, by weight. The experiment included substituting wood fiber in LCPC with 25, 50, 75, and 100 percent (by weight) cotton burr (CB) and cotton burr mixed with 2 percent (by weight) second-cut linters (CBL), respectively, with the remaining fraction as wood fiber and comparing it against the control (100% wood). Samples were extruded into rectangular profiles and tested for physical and mechanical properties such as specific gravity (SG), water absorption, thickness swelling, coefficients of linear thermal expansion (CLTE), flexural strength and modulus, compressive strength, hardness, and nail withdrawal force (NWF). The CB and CBL treatments exhibited SG, CLTE, hardness, and NWF comparable to the control. However, the water absorption and thickness swelling, flexural strength and modulus, and compressive strength all deteriorated at high substitution rates of CB and CBL. The favorable properties of cotton burr included its tendency to decrease CLTE and increase hardness of LCPC.