The inability to be pregnant after at least 12 months of unprotected sexual activity is a sign of infertility, which can affect either the male or female reproductive system. The aim of this work was to compare between Pentoxifylline (PX) versus Platelet-activating factor (PAF) and Caffeine liquid (CL) on sperm activation in Asthenozoospermia casas.In this clinical experiment with a prospective randomized double blind design, 82 male infertile couples who had been having regular sex for at least two years participated, all patients were Asthenospermia according to WHO criteria 2010 aged from 22 to 47 years old, normal ejaculates will serve as the study's sperm supplies. Each sample was divided into three tubes and control tube named Group (1): Control. Group (2): PX. Group (3): PAF. Group (4): CL. The results indicated that adding CL to the semen resulted in an increase in the sperm motility after one hour. However, that significance faded on the subsequent readings. Adding PAF led to a significant increase in sperm motility but less than CL. Adding PX led to a significant increase in sperm motility but less than PAF. Motility decreased after one hour. However, it was significantly better than the baseline. At the two and three hours readings, motility became less than the first hour. In conclusions CL has more pronounced and durable effect on sperm activation in Asthenospermia cases than of PX and PAF. It is better to use semen prepared by CL within one hour of preparation, as it has more pronounced and durable effect within this period.