Background: Somatostatin analogue-based radionuclide therapy with Lu-177-DOTATATE is an important treatment option for patients with advanced neuroendocrine tumours overexpressing somatostatin receptors. In addition to the kidneys, the bone marrow is a major dose-limiting organ. The correlation between developed haematological toxicity and absorbed dose to the bone marrow is poor, which indicates that other factors affect haematological response. The spleen has an important role in the haematopoetic system, including being a reservoir for blood cells. It is also the organ that receives the highest mean absorbed dose during Lu-177-DOTATATE treatment. The aim of this study was to analyse mean absorbed dose to the spleen and its correlation with haematological toxicity, and to explore changes in splenic volume. The study included 41 patients treated with 7.2 GBq (3.5-8.3 GBq) of Lu-177-DOTATATE on two to five occasions. Following each fraction, planar whole-body scans were acquired at 2, 24, 48, and 168 h, and a SPECT/CT at 24 h post-injection. Mean absorbed spleen dose was calculated utilising planar images for time-activity data and SPECT to adjust activity amounts. Splenic volume information was collected from diagnostic CT scans at baseline and follow-up. Results: Median and total absorbed spleen doses were estimated to 4.5 and 15 Gy, respectively. Total absorbed spleen dose correlated with decrease in Hb (p = 0.02), but not WBC (p = 0.31) or PLT (p = 0.65) counts. For patients without bone metastases, mean absorbed spleen dose correlated with decrease in PLT (p = 0.04) but not Hb (p = 0.16) or WBC (p = 0.42) counts. The spleen volume was reduced to 75 % (p < 0.001) of original values (200 vs. 260 ml) at a mean followup of 36 months. Conclusions: Haematological toxicity according to Hb counts was moderately but significantly correlated with total absorbed spleen dose. This supports the possibility that radiation exposure of the spleen affects overall haematological response during Lu-177-DOTATATE treatment.