BACKGROUND Indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), platelet distribution width (PDW), and red cell distribution width (RDW) are considered new markers of the systemic inflammatory response (SIR), and have been widely implemented for the diagnosis of patients with inflammatory diseases. These new indicators have also been widely investigated in preeclampsia (PE) but less analyzed in hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome. AIM To compare SIR markers among HELLP patients, PE only patients, and healthy gravidae. METHODS This retrospective case-control study enrolled 630 cases, including 210 patients with HELLP syndrome (HELLP group), 210 patients with only PE (PE group) and 210 healthy gravidae (control group). The three groups were matched by age, parity, status of assisted reproduction, and multiple pregnancies. Birthweight, gestational age at complete blood count collection, gestational age at delivery, mode of delivery, etc. were recorded. The main indices as NLR, PLR, MPV, PDW, and RDW among the groups were compared, as well as some secondary outcomes including neutrophil, platelets, and hemoglobin . RESULTS The NLR (6.4 vs 4.3 vs 3.5), MPV (11.9 v s 11.2 vs 10.7), PDW (16.4 vs 13.3 vs 14.2), leukocyte (12.4 × 109/L vs 9.7 × 109/L vs 8.7 × 109/L) and neutrophil count (9.9 × 109/L vs 7.3 × 109/L vs 6.1 × 109/L) were highest in the HELLP group, lower in the PE group, and lowest in the control group. Both the overall comparisons between the three groups (all b P < 0.01) and pairwise comparisons between every two groups elicited statistically significant differences (all d P < 0.01, except control vs PE: c P < 0.05 in PDW). The average lymphocyte counts were 1.4 (1.1, 2.0) × 109/L in the HELLP group, 1.6 (1.3, 2.0) × 109/L in the PE group and 1.7 (1.4, 2.0) × 109/L in the control group. The overall comparison of lymphocyte count within the three groups had statistically significant differences ( P = 0.000). The pairwise comparisons between every two groups demonstrated that the HELLP group had a lower lymphocyte count than both the PE ( P = 0.019) and control groups ( P = 0.000), but the difference between the PE and control groups was not statistically significant ( P = 0.432). The overall comparisons on platelet counts and the PLR among these three groups also showed statistically significant differences (both P = 0.000), from low to high being those in the HELLP group (43.4 × 109/L, 64.0), control group (180.5 × 109/L, 103.6) and PE group (181.5 × 109/L, 112.8). Pairwise comparisons of neither index displayed statistically significant differences between the PE and control groups (both P > 0.05), while the differences in the two indices between the HELLP group and the two other groups were still statistically significant (all P = 0.000). RDW values were highest in the HELLP group (14.5% [13.6, 15.3]), lower in the control group (14.1% [13.5, 14.8]) and lowest in the PE group (13.9% [13.4, 14.9]). The difference between the PE and control group did not show statistical significance ( P = 1.000), while RDW values in the HELLP group were higher than those in the other two groups (c P < 0.05 vs control, d P < 0.01 vs PE). CONCLUSION SIR markers such as NLR, RDW, MPV, and PDW were increased and PLR was decreased in HELLP. These SIR markers may become new indicators in the evaluation of HELLP syndrome.