We report abnormal maternal laboratory parameters in twin-to-twin transfusion syndrome (TTTS) at mid-pregnancy. A retrospective chart review was undertaken of 109 patients with TTTS evaluated for placental laser surgery. Complete blood count (CBC), blood type and Rh factor, urine analysis and serum chemistry panel were obtained preoperatively, with the CBC and serum albumin repeated on the first postoperative day. The mean gestational age was 21.2 ± 1.7 weeks. Initial abnormal values included hematocrit (32.1 ± 3.0%), hemoglobin (11.0 ± 1.03 g/dl), serum magnesium (1.71 ± 0.17 mg/dl), total protein (6.08 ± 0.55 g/dl) and albumin (3.06 ± 0.34 g/dl). Despite minimal blood loss and conservative fluid replacement mean hematocrit, hemoglobin, and albumin were 27.3 ± 2.74%, 9.3 ± 0.94 g/dl and 2.56 ± 0.23 g/dl, respectively on postoperative day one. Weight gain (8.0 ± 5.5 lb.) and low urinary output were characteristic peri-operative events. Maternal hypoproteinemia and anemia occur in TTTS at mid-pregnancy. This may contribute independently to amniotic fluid production rates in the fetuses, and explain in part the maternal sensitivity to intravenous fluids in multiple pregnancy. Twin Research (2000) 3, 113–117.