Spaceflight causes alterations in human immunity, a finding which has been well documented immediately following spaceflight. Limited in-flight studies have also confirmed that to some degree immunity is compromised during spaceflight. A comprehensive understanding of the nature of these immune changes is lacking."

Source : Stress Challenges and Immunity in Space pp 259-275

Currently, astronauts returning from stays at the International Space Station are routinely quarantined until their immune system has recovered sufficiently.

Numerous studies have indicated that spaceflight results in dysregulation of the human immune system. This phenomenon has been well documented following flight, where landing and readaptation are significant stressors. More recent data, particularly studies onboard ISS, indicate that this phenomenon persists for the duration of a 6-month orbital spaceflight. Persistent decrements in the function of specific innate or adaptive immune cells, or alterations in cytokine production profiles, could result in clinical risk to crewmembers participating in exploration-class space missions."

Source : Stress Challenges and Immunity in Space pp 205-220

There is as yet no (agreed) explanation as to why the human immune system becomes suppressed in microgravity environments.

Space flights are now known to lead to a wide range of potentially serious health challenges, including loss in bone density and muscle mass, spaceflight-associated neuro-ocular syndrome (SANS), perturbed immune function, and spaceflight anemia. For full technical details, see the 2024Space Omics and Medical Atlas.

Also see:
Apollo Syndromeplugin-autotooltip__plain plugin-autotooltip_bigApollo Syndrome

A 2016 study into cardiovascular disease (CVD) amongst members of the NASA Apollo missions found that the CVD mortality rate in Apollo lunar astronauts was 4–5 times higher than in non-flight and Low Earth Orbit astronauts.

"[...
Spaceflight-associated neuro-ocular syndrome (SANS)plugin-autotooltip__plain plugin-autotooltip_bigSpaceflight-associated neuro-ocular syndrome (SANS)

Approximately 60% of the crew members of the International Space Station have reported altered visual acuity after long-duration exposure to micro-gravity.

"Astronauts on long-duration spaceflight missions may develop changes in ocular structure and function, which can persist for years after the return to normal gravity.
Spaceflight anemiaplugin-autotooltip__plain plugin-autotooltip_bigSpaceflight anemia

"Anemia in astronauts has been noted since the first space missions, but the mechanisms contributing to anemia in space flight have remained unclear."

Source : Nature Medicine volume 28, pages 59–62 (2022)"

Anomalies in the amount of hemoglobin degradation in astronauts (around 12% higher than normal) was first discovered in the 1980s. The degradation leads to anemia, and tends to take hold in the first 10 days or so of micro-gravity spaceflight. After-effects appear to be…