Objectives There are few reports about the effect of CD4/CD8 ratio on the infection of HIV with sepsis. Here we analyze the correlation between the baseline CD4 / CD8 ratio and the pathogenic spectrum of AIDS patients with sepsis and the effect on the prognosis. Methods A retrospective analysis study(May 2010 to June 2017) was carried out using routinely colleted data from HIV with spesis at Chengdu Public Health Clinical Center. The values of clinical data, CD4/CD8 ratio and pathogenic spectrum were evaluated in the study. Results Among 322 positive blood culture HIV patients with septicemia, 208 (64.60%) were fungal infection, 64 (19.90%) were gram-negative bacterial infection, 47 (14.60%) were Gram-positive bacterial infection, and 3 (0.90%) were fungal and bacterial infection. Among the fungal infections, Cryptococcus was found in 152 cases (73.08%), followed by cyanobacteria marneffei in 53 cases (25.48%) and Candida in 3 cases (1.44%); Salmonella in 38 cases (59.38%) and Escherichia coli in 17 cases (26.56%); Staphylococcus in 28 cases (59.58%) were positive. When the CD4 / CD8 ratio≤0.3, the risk of sepsis infection was significantly higher than that of CD4 / CD8 > 0.3. The lower the ratio of CD4 / CD8 (< 0.1), the higher the risk (χ 2 =188.968,P = 0.00).When the ratio of CD4 / CD8 was less than or equal to 0.3, the incidence of fungal infection was significantly increased (67.14%), and the incidence of gram-negative bacterial infection (18.02%) was significantly higher than that of Gram-positive bacterial infection (13.78%), (χ 2 = 283.277, P = 0.00); when the ratio of CD4 / CD8 was greater than or equal to 0.3, the incidence of septicemia was significantly reduced, and there was no significant difference between the original spectrum of infection (χ 2 = 1.750, P=0.42)。 286 patients (88.82%) were discharged after treatment, 36 patients (11.18%) died after treatment. Conclusions In Chengdu of China, the main pathogens of septicemia in AIDS patients are fungi, including Cryptococcus and cyanobacteria marneffei, next are bacteria containing Salmonella and Staphylococcus. The lower the ratio of CD4 / CD8, the higher the risk of infection with sepsis, the higher the risk of multiple infection, and the higher the mortality. Therefore, we think that CD4 / CD8 ratio is an important risk factor for HIV infection with septicemia. We should pay more attention to role of the CD4 / CD8 ratio in clinical work, and it may be help us predicting progress of HIV disease.