Background Blood platelet levels are being evaluated as predictive and prognostic indicators of the severity of malaria infections in humans. However, there are few studies on platelets and Plasmodium falciparum malaria during pregnancy. Methods A case–control study was conducted at Gadarif Hospital in Eastern Sudan, an area characterized by unstable malaria transmission. The aim of the study was to investigate thrombocytopenia in pregnant women with P. falciparum malaria (cases) and healthy pregnant women (controls). Results The median (interquartile) platelet counts were significantly lower in patients with malaria (N = 60) than in the controls (N = 60), 61, 000 (43,000–85,000) vs. 249,000 (204,000–300,000)/μL, respectively, p < 0.001. However, there was no significant difference in the platelet counts in patients with severe P. falciparum malaria (N = 12) compared with those patients with uncomplicated P. falciparum malaria (N = 48), 68, 000 (33,000-88,000)/μL vs. 61, 000 (45,000–85,000)/μL, respectively, p = 0.8. While none of the control group had thrombocytopenia (platelet count <75, 000/μL), it was found that 6/12 (50%) and 27/48 (56.2%) (p <0.001) of the patients with severe malaria and uncomplicated malaria had thrombocytopenia, respectively. Pregnant women with P. falciparum malaria, compared with the pregnant healthy control group, were at higher risk (OR = 10.1, 95% CI = 4.1–25.18; p < 0.001) of thrombocytopenia. Two patients experienced bleeding, and there was one maternal death due to cerebral malaria where the patient’s platelet count was only 28,000/μL. Conclusion P. falciparum malaria is associated with thrombocytopenia in pregnant women in this setting. More research is needed.