Objectives To evaluate umbilical cord immune cells in pregnancies with autoimmune disorders (AID) and/or methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Methods Umbilical cords were obtained from seven AID women without MTHFR polymorphisms, eight with AID and MTHFR polymorphisms, nine with MTHFR polymorphisms, and eight with neither. Umbilical cords were assessed immunohistologcally by anti-CD4, anti-CD8, anti-CD14, anti-CD19, anti-CD21, and anti-CD56 antibodies in six umbilical cord zones: 1) arterial wall 2) periarterial zone 3) venous wall 4) perivenous zone 5) intervascular zone, and 6) subamniotic zone. Results AIDs and MTHFR polymorphisms had an effect on the number and composition of CD4+ cells in the venous wall. The presence of a MTHFR polymorphism may affect the number and morphology of CD4+ cells in the subamniotic zone. CD8+ cell distribution is substantially influenced by the presence of maternal risk factors. The co-existence of AID with MTHFR polymorphism has a prominent effect on the number and morphology of CD14+ cells, especially in the arterial wall. CD19+ cells were only observed in the control group in the venous wall, perivenous zone, and intervascular zone. CD21+ cells were only observed in the arterial wall of the control group and the intervascular zone of the AID group with different morphologic features. The number and morphology of CD56+ cells is prominently affected by the presence of maternal risk factors. Conclusions Umbilical cord stem cell and immune cell composition may be affected by the presence of risk factors like MTHFR polymorphisms and/or AID.