diff --git a/config/cmake/ConfigureChecks.cmake b/config/cmake/ConfigureChecks.cmake
index ef8500c2559..aea3fd62443 100644
--- a/config/cmake/ConfigureChecks.cmake
+++ b/config/cmake/ConfigureChecks.cmake
@@ -905,12 +905,24 @@ if (${HDF_PREFIX}_SIZEOF__FLOAT16)
     # compile a program that will generate these functions to check for _Float16
     # support. If we fail to compile this program, we will simply disable
     # _Float16 support for the time being.
+
+    # Some compilers, notably AppleClang on MacOS 12, will succeed in the
+    # configure check below when optimization flags like -O3 are manually
+    # passed in CMAKE_C_FLAGS. However, the build will then fail when it
+    # reaches compilation of H5Tconv.c because of the issue mentioned above.
+    # MacOS 13 appears to have fixed this, but, just to be sure, backup and
+    # clear CMAKE_C_FLAGS before performing these configure checks.
+    set (cmake_c_flags_backup "${CMAKE_C_FLAGS}")
+    set (CMAKE_C_FLAGS "")
+
     H5ConversionTests (
         ${HDF_PREFIX}_FLOAT16_CONVERSION_FUNCS_LINK
         FALSE
         "Checking if compiler can convert _Float16 type with casts"
     )
 
+    set (CMAKE_C_FLAGS "${cmake_c_flags_backup}")
+
     if (${${HDF_PREFIX}_FLOAT16_CONVERSION_FUNCS_LINK})
       # Finally, MacOS 13 appears to have a bug specifically when converting
       # long double values to _Float16. Release builds of the dt_arith test
@@ -919,12 +931,19 @@ if (${HDF_PREFIX}_SIZEOF__FLOAT16)
       # simply chopping off all the bytes of the value except for the first 2.
       # These tests pass on MacOS 14, so let's perform a quick test to check
       # if the hardware conversion is done correctly.
+
+      # Backup and clear CMAKE_C_FLAGS before performing configure checks
+      set (cmake_c_flags_backup "${CMAKE_C_FLAGS}")
+      set (CMAKE_C_FLAGS "")
+
       H5ConversionTests (
           ${HDF_PREFIX}_LDOUBLE_TO_FLOAT16_CORRECT
           TRUE
           "Checking if correctly converting long double to _Float16 values"
       )
 
+      set (CMAKE_C_FLAGS "${cmake_c_flags_backup}")
+
       if (NOT ${${HDF_PREFIX}_LDOUBLE_TO_FLOAT16_CORRECT})
         message (VERBOSE "Conversions from long double to _Float16 appear to be incorrect. These will be emulated through a soft conversion function.")
       endif ()