Objective To investigate clinically severe malaria patients with Plasmodium falciparum (P. falciparum), Plasmodium vivax (P. vivax) and mixed species infections. Methods This study was conducted at Dr. Saiful Anwar General Hospital, Malang, Indonesia, from December 2011 to May 2013. Twenty nine patients (mean age of 41 years, 22% female), who suffered from severe malaria according to World Health Organization criteria (major and minor) and other criteria based on previous studies, were selected by consecutive sampling. Blood samples were obtained at admission from peripheral blood for microscopic diagnostic, nested PCR and laboratory examination of blood chemistry. Laboratory results were compared between the groups and correlated to each other. Results From 29 samples, eight (28%) were diagnosed as P. falciparum mono-infection, 12 (41%) as P. vivax mono-infection and nine (31%) as mixed infections, confirmed by PCR. Cerebral malaria occurred in P. falciparum or mixed species infection only. Parasitaemia was highest in P. falciparum mono-infection. Mean haemoglobin was significantly lower in P. falciparum than P. vivax infection (P = 0.01). Mean thrombocyte count (77 138/μL) was low in all groups. Mean urea, creatinine, total and direct bilirubin were significantly higher in P. falciparum mono-infection compared to other groups, whereas aspartate aminotransferase and alanine aminotransferase showed no significant differences. Parasitaemia was positively correlated with an increase in urea, creatinine, bilirubin and leucocytosis in all species. Conclusions Both Plasmodium species can solely or in combination cause severe malaria. Mixed infection was generally more benign than P. falciparum mono-infection and seemed to have some protective effects.